DFM3-2

Question 1

1) Ion channels are divided into two main classes: gated- and non-gated channels. Which of the following statement(s) is (are) correct: (2 p)
a) Gated channels can only be activated by stimuli acting from the outside of neurons
b) Non-gated ion channels require energy to allow ions to pass through
c) Ionotropic ion channels belong to the gated ion channel class
d) Both gated- and non-gated ion channels contribute to setting the resting membrane potential of neurons
e) Some gated ion channels become inactivated with a prolonged stimulation

Answer 1

c) Ionotropic ion channels belong to the gated ion channel class
e) Some gated ion channels become inactivated with a prolonged stimulation

Question 2

2) The passive membrane properties of neurons determine the efficacy of summation of synaptic inputs. Which of the following statement(s) is(are) correct: (2 p)
a) The amplitude of action potentials is determined by the neuron’s time and space constants
b) Synaptic summation is more efficient with higher time and space constants
c) The time and space constants affect the action potential propagation and release oftransmitters from axon terminals
d) The time and space constants only influence sub-threshold postsynaptic potentials
e) The time and space constants are larger at more hyperpolarized membrane potentials

Answer 2

b) Synaptic summation is more efficient with higher time and space constants
d) The time and space constants only influence sub-threshold postsynaptic potentials

Question 3

An action potential (AP) transmits the electrical signals along the axons of neurons. Which of the following statement(s) is(are) correct: (2 p)

a) The electrical signal of an AP is converted to a chemical signal at synapses with only electrical transmission via gap junctions
b) During an action potential, all voltage-gated channels can be activated
c) Action potentials unidirectional propagation is controlled by sodium channel inactivation
d) The afterhyperpolarization is mediated by both voltage- and ligand-gated K+ channels
e) The frequency of action potential firing is always constant for each neuron

Answer 3

b) During an action potential, all voltage-gated channels can be activated
c) Action potentials unidirectional propagation is controlled by sodium channel inactivation
d) The afterhyperpolarization is mediated by both voltage- and ligand-gated K+ channels

Question 4

4) All neurons have a resting membrane potential (RMP) around -65 mV. Which of the following statement(s) is(are) correct: (2 p)
a) The driving force of ions helps setting the RMP
b) The difference in permeability of ions is important in setting the RMP
c) The permeability of Na vs K does not play an important role in setting the RMP
d) The RMP does not influence the direction of ion flux through ion channels
e) The RMP is the same for all neurons in the brain

Answer 4

a) The driving force of ions helps setting the RMP
b) The difference in permeability of ions is important in setting the RMP

Question 5

Chemical synapses exhibit plasticity which means that they can either be strenghtened or weakened. Such synaptic plasticity can last for different periods of time. In this question you should mention three types of synaptic enhancement (i.e. strengthening) that differ in duration.

A) Mention a type of strengthening that lasts for milliseconds to seconds and describe briefly the underlying mechanism (2p).

B) Mention a type of strengthening that lasts for up to a few hours and describe briefly the underlying mechanism (3p).

C) Mention a type of strengthening that lasts for days, weeks or even longer and describe briefly the underlying mechanism (3p).

Answer 5

Answer: Facilitation. It is due to successive accumulation of calcium in the presynaptic terminal during repetitive action potential stimulation

Answer: The early phase of long-term potentiation (LTP). It is triggered by brief high-frequency trains of action potentials that leads to opening of voltage-sensitive NMDA channels giving rise to calcium influx. This results in activation of kinases that eventually give rise to insertion of more AMPA receptors in the postsynaptic membrane (by exocytosis)

Answer: The late phase of long-term potentiation (LTP). It is also triggered by brief high- frequency trains of action potentials that leads to opening of voltage-sensitive NMDA channels giving rise to calcium influx. This results in activation of kinases that eventually cause activation of transcription factors (such as CREB) resulting in increased expression of different genes encoding synaptic proteins. Thereby synapses can be enlarged and/or new synapses can form.

Question 6

1) Which type of primary afferent fibre mediates:

a) first pain?
b) second pain? (2p)

Answer 6

1) a) A-delta fibre (1p), b) C-fibre (1p).

Question 7

There are two major ascending nociceptive (“pain”) pathways within the spinothalamic tract (anterolateral system), one sensory-discriminative (neospinothalamic) and one affective- motivational (paleospinothalamic).

a) Which one sends major input to the thalamic ventral posterior lateral nucleus and then primary somatosensory cortex (S1)?
b) Which one sends major input to the medial thalamic nuclei and then anterior cingulate cortex and insula? (2p)

Answer 7

a) The sensory-discriminative (neospinothalamic) pathway (1p),
b) affective-motivational (paleospinothalamic) tract (1p).

Question 8

Sensitization is defined as increased responsiveness of nociceptive neurons to their normal input, and/or recruitment of a response to normally subthreshold inputs. It is also pointed out that spontaneous discharges and increases in receptive field size may occur. Name the corresponding perceptions that would be expected to result from:

a) increased response of nociceptive neurons to their normal input
b) recruitment of a response to normally subthreshold inputs (=lowered threshold)
c) spontaneous discharges? (3p)

Answer 8

a) hyperalgesia (1p),
b) allodynia (1p),
c) ongoing pain (1p).

Question 9

A patient complains of pain in the right shoulder. He tells you that on good days, when shoulder pain is relatively mild, it stays localized to the shoulder, but on days with more intense shoulder pain he feels pain also in his upper arm, and during very high intensity of shoulder pain also in his lower arm and fingers. What kind of pain is this is a typical description of? (1p)

Answer 9

Referred pain (1p).

Question 10

Stimulating a rod with light leads to membrane hyperpolarization. Explain the details of phototransduction in the rods. (4p)

Answer 10

Absorption of light by the rods causes a configuration change from 11-cis to all-trans retinal which in turn activates a G-protein, transducin, that then leads to an activation of phosphodiesterase. The phosphodiesterase hydrolyzes cGMP leading to a closure of the Na+ channel and hyperpolarization.

Question 11

The pupillary light reflex causes a decrease in the diameter of the pupil that follows light stimulation of the retina. Describe the anatomical pathway that regulates this reflex. (3p)

Answer 11

Projections from the retina to the pretectum and bilateral projections to the Edinger- Westphal nucleus. Neurons in the Edinger-Westphal nucleus send bilateral axons via the oculomotor nerve to terminate in the ciliary ganglion that innervates the constrictor muscle in both eyes.

Question 12

You are examining the pupillary light reflex in a patient. When you stimulate the left eye with light the pupil in the left eye decreases in diameter but NOT the right pupil. Explain the reason for this. (1p)

Answer 12

A problem with the oculomotor nerve.

Question 13

Mark the following statements as true or false. For a correct marking you get +0.5 p, for an incorrect marking you get -0.5 p. If you mark do not know it gives 0 p. total 3p

1. Blood to the hand region of M1 is mostly supplied by a. cerebri anterior
2. Nucleus caudatus is located medial to capsula interna
3. The decussation of the pyramidal tract occurs in capsula interna
4. The alpha-motor neurons are located in the ventral horn
5. The superior colliculus is important for eye movements
6. Thalamus is located lateral to capsula Interna

Answer 13

1. false
2. true
3. false
4. true
5. true
6. false

Question 14

B) Explain how motor information is sent to the cerebellum and then back to the cortex. Which white mater tracts are involved and what “relay stations” are involved? 4p

Answer 14

Sent from cortex to the pons. Next neuron takes it from the pons decussates and ends in the cerebellar cortex. From there to the deep nuclei (nucleus dentatus) and then via the superior cerebellar peduncle to the ventral lateral nucleus of the thalamus. Then back to the cortex.

Question 15

Which of the following statements about the primary motor cortex are correct? (2 p)

a) The primary motor cortex (M1) lacks direct projections to the spinal cord.
b) Histologically, M1 is characterized by large pyramidal neurons (Betz cells) in layer V.
c) Surgical removal of M1 impairs postural control, but leaves hand motor skills such as

object manipulation virtually intact.

d) M1 is somatotopically organized.

Answer 15

b) Histologically, M1 is characterized by large pyramidal neurons (Betz cells) in layer V.
d) M1 is somatotopically organized.

Question 16

In several brain regions, including the ventral premotor cortex, we find an interesting type of neuron which is active both during the performance of an act, and when we watch someone else perform the same act. What are these neurons called? (1 p)

Answer 16

Mirror neurons

Question 17

Many studies, using different methodological approaches, show that the supplementary motor area (SMA) is important for the learning and performance of movement sequences. Please give two examples of research findings that support this notion. (2 p)

Answer 17

Surgical removal of the SMA in the monkey specifically impairs performance and relearning of previously learned sequences.

Human patients with SMA lesions have difficulties performing movement sequences from memory.

Electrophysiological studies in the monkey demonstrate that many neurons in the SMA arespecifically active during different phases of sequence performance.

Neuroimaging studies in humans demonstrate that the SMA is activated during sequence performance (and that the activity in this region is related to sequence structure).

Question 18

Which of the following statements about the dorsal premotor cortex (PMD) are correct? (2 p)

a) The PMD is located on the dorsolateral surface of the precentral gyrus.
b) The PMD plays important roles for sensory guided behaviors, such as reaching for an object or selecting between different behaviors based on sensory cues.
c) The PMD has no connections with M1, nor with the SMA.
d) The PMD is a uniquely human motor area with no counterpart in the monkey.

Answer 18

a) The PMD is located on the dorsolateral surface of the precentral gyrus.
b) The PMD plays important roles for sensory guided behaviors, such as reaching for an object or selecting between different behaviors based on sensory cues.

Question 19

a) What parts of the prefrontal cortex and cingulum are involved in emotion regulation? (1p)

Answer 19

Orbitofrontal PFC/mPFC and anterior/rostral Cingulum

Question 20

What parts of the prefrontal cortex and cingulum are involved in non-emotional regulation? (1p)

Answer 20

Dorsolateral PFC and caudal Cingulum

Question 21

What kind of attentional problems can arise from cortical leasons in the right parietal lobe? (1p)

Answer 21

: can lead to left hemispatial neglect syndrome (spatial neglect is also correct)

Question 22

d) Describe at least two characteristics of the differences between top-down (endogenous) v.s. stimulus-driven (exogenous) driven attention. (2p)

Answer 22

Top-down regulated attention is controlled, slower, has limited capacity, and needs effort. Top-down related attention is also part of working memory.

Stimuls-driven attention is fast, has near to unlimited capacity, needs little effort and hard to change.

Question 23

e) Some brain functions are lateralized. Name two functions that are lateralized and the central brain areas for these functions. (2p)

Answer 23

• Language is lateralized so that about 90% of right handed people have their language centers, Broca’s and Wernicke’s area, in the left hemisphere. Only about 50% of left handed people have this laterialization, both symmetric and right-hemsphere representation is more common in this group.
• Somatosensory and motor processing is lateralized, so that information from the right side of the body is processed in the left hemisphere and vice versa. This is also roughly true for other sensory functions, but a bit more complex, for example, for the eyes, this lateralization is related to the visual field rather than the eyes.
• There is some support for the brain hemispheres to have different perceptual processing styles so that left hemisphere processing is more focused on details (local processing) while right hemisphere processing is disposed to be more holistic (global processing).
• The right parietal lobe is in most individuals more involved in spatial attention than the left hemispehere.

Question 24

a) The Mesolimbic dopamine system is believed to play an important part in the reward system. Which brain regions are part of the mesolimbic dopamine system? Give evidence for this hypothesis. (3p)

Answer 24

Response: Ventral Tegmental Area (VTA) and nucleus accumbens/ventrala striatum. Evidence: “In principle, all addictive agents increase dopamine levels in this system. - Also natural rewards (like sex) activate this system.

• Dopamine neurons that originate from these areas and that project to nucleus accumbens regulate “salience” (motivation and desire), which is important input for choosing between different behaviors.
• Rats learning self-administration of drugs stop taking them if you block dopamine receptors at the nucleus accumbens with a D2-receptor antagonist.

Question 25

b) Which role does the mesolimbic dopamine system play in addiction? (1p)

Answer 25

It is important for learning which stimuli that gives reward, i.e. it is central for associating the drug with pleasure. Additionally, the activity of this system increases when a drug dependent person sees something that he / she associates with drug intake, eg cues that are correlated to drug craving. This is also called “wanting” and differs from “liking” that corresponds tothewell-being/rushyougetfromthedrug. Inaddition,addiction(andabuse)overtimeoften leads to a downregulation of the dopaminergic system, which results in the need to increase the dose to get the same effect.

Question 26

1) Action potential are electrical events that transmit signals along the axons of neurons. Their generation and propagation require an interplay between different ion channels and their properties. Which of the following statement(s) is (are) correct: (2 p)
1. Na+ channel inactivation determines the shape, but not the propagation of action potentials
2. The fast activation of Na+ channels and their inactivation are essential for the generation of action potentials
3. All ion channels undergo inactivation
4. All voltage-gated channels present in a neuron can be activated by an action potential
5. Both voltage- and ligand-gated K+ channels underlie the afterhyperpolarizations

Answer 26

2 The fast activation of Na+ channels and their inactivation are essential for the generation of action potentials

4 All voltage-gated channels present in a neuron can be activated by an action potential

5 Both voltage- and ligand-gated K+ channels underlie the afterhyperpolarizations

Question 27

Passive membrane properties determine the way neurons integrate synaptic inputs. Which of the following statement(s) is (are) correct: (2 p)

a) Neurons’ time and space constants are determined by voltage-gated ion channels
b) The time and space constants play a key role only at subthreshold membrane potentials, that is when neurons are not firing action potentials
c) EPSPs with large amplitudes will always summate efficiently to produce an action potential regardless how short the time and space constants are
d) Small EPSPs can summate more efficiently if they occur in neurons with long space and time constants
e) The time and space constants determine the shape and the propagation of action potentials

Answer 27

b) The time and space constants play a key role only at subthreshold membrane potentials, that is when neurons are not firing action potentials
d) Small EPSPs can summate more efficiently if they occur in neurons with long space and time constants

Question 28

The electrical activity of neurons is generated by flow of ions through ion channels. Which of the following statement(s) is (are) correct: (2 p)

a) The structure of ion channels determines the direction of the flow of ions
b) The opening and inactivation of an ion channel are mediated by conformational changes occurring at different parts of a channel
c) The direction of the flow of ions is determined by the driving force, which is independent of the channel itself
d) All gated channels contribute to the generation of action potentials
e) The resting membrane potential is determined by both gated and non-gated ion channels

Answer 28

b) The opening and inactivation of an ion channel are mediated by conformational changes occurring at different parts of a channel
c) The direction of the flow of ions is determined by the driving force, which is independent of the channel itsel

Question 29

The firing frequency of action potentials is an important way by which neurons encode information within the nervous system. Which of the following statement(s) is (are) correct: (2 p)

a) The firing frequency of action potentials does not vary among neurons
b) The amplitude of the slow afterhyperpolarization can affect the firing frequency of action potentials
c) The firing frequency of neurons increases with the strength of excitatory synaptic inputs
d) Leak channels have a strong and direct influence on the firing frequency of neurons
e) Ca2+ influx can indirectly affect the firing frequency of neurons

Answer 29

b) The amplitude of the slow afterhyperpolarization can affect the firing frequency of action potentials
c) The firing frequency of neurons increases with the strength of excitatory synaptic inputs
e) Ca2+ influx can indirectly affect the firing frequency of neurons

Question 30

Neurons use a variety of different neurotransmitters. This theme deals with the important neurotransmitter acetycholine.

a) Mention a neuron type which uses acetycholine as neurotransmitter? 1p b) In which type of vesicle is acetycholine stored? 1p
c) On which two main types of postsynaptic receptor does acetycholine act? Both the names and types of receptor are required for 2p
d) How is acetylcholine inactivated? 1p
e) Inhibition of this inactivation mechanism can be used clinically –which type of drug and/or which disease does it regard? A correct type of drug or a correct disease is sufficient for 1p
f) Inhibition of this inactivation mechanism can also be used with deleterious effects in war or in terrorist-attacks – by which compound and/or mechanism? Either a compound or a mechanism of action is sufficient for 1p.

Answer 30

a) Motorneurons. Also correct are postganglionic parasympathetic neurons, striatal cholinergic interneurons and cholinergic basal forebrain neurons.
b) It is stored in synaptic vesicles (also called small synaptic vesicles, i.e. not in large dense-cored vesicles)
c) Nicotinic receptors which are ligand-gated ion channels (=ionotropic receptors); Muscarinic receptors which are G-protein-coupled receptors (=metabotropic receptors).
d) It is broken down by the enzyme acetylcholineesterase.
e) Acetylcholineesterase inhibitors (like neostigmine, rivastigmine and donezepil). They are used to treat myasthenia gravis, Alzheimer ́s disease and glaucoma.
f) Nerve gases/nerve agents like sarin, tabun and Novichok block acetylcholineesterase irreversibly which leads to fatal overactivation of acetylcholine receptors. Such an agent (Novichok) was used to posion the former russian agent Sergei Skripal and his daughter Yulia Skripal in Salisbury UK in 2018, and (sarin) in the terror attack in Tokyos subway in 1995.

Atropine can be used as an antidote as it blocks muscarinic acetylcholine receptors.

Question 31

Describe:

a) different types of nociceptors (i.e. free peripheral nerve ending of primary afferent nerve fibers that sense noxious stimuli) and
b) different types of neurons in the dorsal horn that are activated by nociceptive stimulation. Which are the differences between the types of nociceptors and dorsal horn neurons, respectively?

Answer 31

a) Types of nociceptors:

• Unimodal:
  
  • Mechanosensitive – respond to intense mechanical stimulation that threaten to damage the tissue.
  • Thermosensitive – respond to temperatures >42 °C or <17 °C.
  • Chemosensitive – respond to the H +, K +, serotonin, bradykinin etc.
• Polymodal – respond to all types of nociceptive stimuli
• Silent – nerve endings that are normally not responsive to mechanical or thermal stimuli, but that are chemically activated during inflammation and then respond to mechanical and thermal stimuli.

b)

Different types of neurons in the dorsal horn that are activated by nociceptive stimulation:

• Nociceptive specific (NS) neurons – are located in lamina I and have small receptive fields – receive input mostly from A-delta fibers – convey well localized (rapid) pain.
• Polymodal nociceptive neurons – are also located in lamina I but have large receptive fields – receive afference mostly from C-fibers – convey more diffuse (slow) pain.
• “Wide Dynamic Range” (WDR) neurons – receive input from both nociceptive and non- nociceptive afferents – lies in lamina 5 and has large receptor fields – convey more diffusely localized pain – some of them from visceral organs – possible substrate for referred pain.

Question 32

a) There are 3 papillae on the surface of the tongue. Describe their location on the tongue and the taste or tastes that dominate for the papillae. What cranial nerve innervates these different regions of the tongue? (6p)
b) Stimulus-coupled depolarization for bitter tastes and amino acids (umami) relies on the same PLCβ2/IP3/TRPM5 dependent mechanism. How do we then distinguish between umami and bitter tastes? (2p)

Answer 32

a) Circumvallate, bitter, 48%, glossopharyngeal (IX); Foliate, sour, 28%, glossopharyngeal(IX); Fungiform, sweet and salty, 24%, facial nerve (VII)
b) Differentiation occurs at the receptor level and separate channels for the relay of this information to the brain. The bitter tastes use T2R receptors while umami uses T1R1 and T1R3.

Question 33

a) The corticospinal tract runs from cortex cerebri to medulla spinalis. Describe how these axons go from the cortex to reach the location of the spinal cord that controls the muscles of the hand. Give the correct anatomical names for the different locations. 3 p
b) Describe briefly how the axons of the corticospinal tract receive their blood supply. 2p

Neuro histology:

c) Describe what this image represents. (1p)
b) Where in the CNS are the cell bodies giving rise to the nervous component on the picture localized (give a specific location)? (0,5p)
c) Give a suggestion to how these cells can be identified in a histological section. (0,5p)

Answer 33

a) The axon then pass through the capsula interna, that continues trough the ventral mesencephalon as the crus cerebri. They then continue through the ventral pons. They emerge on the ventral side of medulla oblongata as the pyramis medullae oblongata. The majority of the fibers will cross in decussation pyramis medullae oblongata and continue in the dorsolateral spinal cord to the cervical region of the spinal cord. There they will reach the ventral horn to control the muscles of the hand.
b) They begin by getting their blood from the carotis interna (mainly from a. cerebri media). This changes at the level of crus cerbri where blood supply changes to the a. vertebralis and a. basilaris system.
c) The neuromuscular junction.
b) In the ventral horn of the spinal cord.
c) Identification of cells by location and morphology (localize ventral side of the spinal cord & find the grey matter, look for cells much larger in size than surrounding cells & irregular shape).

Question 34

In terms of skilled movement, the cerebellum is thought to implement motor learning by continuously comparing a) executive commands arising from the primary motor & prefrontal cortex via the contralateral pons and b) ongoing sensory feedback arising from ascending spinal and vestibular inputs encoding limb positioning and relevant movement parameters. This instantaneous difference gives rise to an error correction signal conveyed by the deep cerebellar nuclei (DCN) neurons, i.e. cerebellar output, which informs cortex via the motor thalamus about discrepancies between desired and actual movement.

a. What inputs do DCN neurons receive and what are the nature of their connection? Sketch the main loops within the cerebellar circuit that controls DCN output. (2p)
b. What inputs do Purkinje neurons receive and what are their connections called? (2p)
c. Motor learning occurs when an error signal is available, hence an elevated level of DCN activity. Describe how this would be accomplished at the neural level. (1p)
d. According to a model proposed by Ito and colleagues, inferior olive input to the cerebellum takes the form of a learning signal associated with motor learning? Describe the molecular basis (3p).

Answer 34

a) Afferent mossy and climbing fibre input (excitatory) and Purkinje input (inhibitory). Sketch Figure 19.10 (right) from 5th edition Purves.
b) Axodendritic input from granule cells referred to the parallel fibre connection. Axosomatic input from Inferior olive cells referred to as climbing fibre input. Local interneurons from Basket, Golgi and Stellate inputs in the cerebellar cortex shape Purkinje activity.
c) Weakening of Purkinje activity will lead to less inhibition exerted on DCN output, thus allowing to discharge at higher spiking frequencies.
d) One way to achieve weakening of Purkinje (P) activity is to induce long-term synaptic depression. This occurs when parallel fibre input is concurrent with climbing fibre input, thus, triggering AMPA internalization because of heightened levels of intracellular calcium hence activating second messenger systems, i.e. Phospho-Kinase C (PKC) pathways that will internalize AMPA receptors causing LTD on Purkinje neurons and reducing their excitability for as long as 20-30 minutes. During this period, DCN activity may increase because of reduced inhibition. Without climbing fibre input, DCN are inhibited by P cells, hence low ‘motor learning’ output coming out of the cerebellum to affect cortical activity.

Question 35

a) Many organisms on the planet have mechanisms assuring a stable diurnal rhythm. What are the main functions of the circadian system in humans? (3 points)
b) Explain how light at different times of the day affects (= “entrain”) the circadian system. The answer should include a description of how light can be used to make a person more of a morning type (rather than an evening type). Also describe other factors that should be considered for effectively entraining (setting) the phase of a person’s circadian rhythm. (4 points)

Answer 35

a) adaptation, anticipation and synchronization.

Synchronization of biological processes in the body so that they are aligned with each other and the environment. This is an adaptation to changes of light/darkness in the environment. The system allows us to not only react but also anticipate and prepare the body for the changes in light/darkness

b Light in the morning shortens the circadian rhythm making a person more of a morning type. Light in the evening/night will delay the rhythm so that a person becomes more of an evening type. Light during the middle day is still supportive of health, but does not cause a delay or shortening of the rhythm. Can also get points for describing the neural mechanisms sensitive to light and keeping the rhythmicity both centrally in the SCN and in cells/organs the periphery – if then also describing how they are entrained/affected by light.

To become more of a morning person: As mich daylight as possible in the morning, in combination with darkness/low light levels in the evening. Other factors include that melatonin can be used (in the early evening), and that one should avoide caffeine late in the evening (causing both a delay as well as pottentially disturbing sleep).

Question 36

Stress is a central function that allows us to adapat and prepare for situations with higher (or expected higher) demands, and involve a number of neural structures. Stress also involves endocrinological, immunological, meatbolic, cognitive (e.g. focus) and behavioral changes.

a) Describe Seyle’s “General Adaptation Syndrome”, and how it relates to health. (1p)
b) Describe the major neural and neuroendocrinological pathways involved in the stress response. This explanation should include how they work in the time domain. Also give an example of a situation and explain how the different stress pathways respond to this. (3p)

Answer 36

a) should include a figure or a description of the 1) alarm reaction and mobilization phase, 2) resistance phase where a person cope with the stressor(s), and 3) and exhaustion phase where resistance is no longer possible

b)

b) Should include a desciption of the very fast response of the Autonomic nervous system (ANS, both the involvement of the parasympathetic nervous system and the sympathetic nervous system). The ANS reacts to acute stress and the changes occur in seconds, the first response being an inhibition of the parasympathetic nervous system, directly followed by an activation of the sympathetic nervous system. This has large effects on our physiology, cognitive functioning and beahviour. For example, the fast ANS affects pupil size, heart rate, blood pressure, hand sweating, gives focus.

The answer should also describe the involvement of the Hypothalamic-pituatiry-adrenal (HPA) axis. The HPA-axis takes longer time to react, normally 20-30 minutes, and regulates many body processes including metabolic, digestion, immune functioning, For example, cortisol assures availability of glucose so that the person has energy to deal with a stressful situation.

Question 37

1) The electrical activity of neurons is generated by ion flow though ion channels. Which of the following statement(s) is (are) correct regarding ion channels: (2 p)
a) The flow of ions through ion channels requires energy in form of ATP
b) Ion channels allow all ions to pass through
c) Ion channels have a selectivity filter to specifically recognize and select a given ion type
d) Ion channels are membrane lipids that allow ion to pass only in one direction
e) The direction of the flux of ion is only determined by the driving force

Answer 37

c) Ion channels have a selectivity filter to specifically recognize and select a given ion type
e) The direction of the flux of ion is only determined by the driving force

Question 38

The resting membrane potential of neurons is around -65 mV and is determined by: (2 p)

a) Passive flow of ions
b) Voltage-gated ion channels
c) Leak K+ and Na+ channels
d) Na/K ATPase
e) Non-gated ion channels

Answer 38

a) Passive flow of ions
c) Leak K+ and Na+ channels
e) Non-gated ion channels

Question 39

Action potentials transmit the electrical signals along the axons of neurons. Which of the following statement(s) is (are) correct: (2 p)

a) Action potentials are generated in the dendrites of neurons
b) There is an influx of Ca2+ via voltage-gated channels during action potentials
c) The rising phase of an action potential is mediated by Ca2+ influx
d) Action potentials propagate from soma to axon terminals with constant amplitude
e) The slow afterhyperpolarization controls the frequency of action potentials

Answer 39

b) There is an influx of Ca2+ via voltage-gated channels during action potentials
d) Action potentials propagate from soma to axon terminals with constant amplitude
e) The slow afterhyperpolarization controls the frequency of action potentials

Question 40

The passive membrane properties of neurons determine the efficacy of summation of synaptic inputs. Which of the following statement(s) is (are) correct: (2 p)

a) The time and space constants does not vary between different types of neurons
b) The spatial summation increases with an increased space constant
c) The temporal summation decreases with increased space constant
d) Neurons with small time and space constants have less efficient summation
e) The shape of action potentials is determined by the time constant of the neuron

Answer 40

b) The spatial summation increases with an increased space constant
d) Neurons with small time and space constants have less efficient summation

Question 41

a) Which is the major inhibitory neurotransmitter in the brain? (1p)
b) Describe how it is synthesized. (2p)
c) Which is the major neurotransmitter in the nigrostriatal and mesolimbic pathways?
d) Describe how it is synthezied. (2p)

Answer 41

a) GABA
b) It is synthesized in inhibitory nerve terminals by conversion of glutamate by the enzyme glutamate decarboxylase (GAD).
c) Dopamine

d)

Tyrosine -> l-dopa -> dopamine

Question 42

When you studied to this exam you used your declarative memory to store a lot of information. The storage of such memories depends on a critical brain region and a certain type of synaptic modification which takes place in this region.

a) Which brain region is particularly critical for storage of declarative memories? (1p)
b) Which synaptic modification in this brain region is important? (1)
c) Describe the mechanisms that underlie this synaptic modification. (4p)

Answer 42

a) hippocampus
b) LTP
c) strong activation of Schaffer collaterals (by high-frequency action optential activity) leads, in the postsynaptic CA1 neurons, to depolarization (by AMPA receptor activation) along with activation of NMDA receptors. The depolarization relieves the voltage-dependent Mg2+ block of the NMDA receptor channels causing Ca2+ to flow in. Ca2+ activates kinases (CaMKII and PKC) that phosphorylate proteins that trigger exocytosis of AMPA receptor-containing vesicles, which leads to incorporation of a larger number of AMPA receptors postsynaptically. In late LTP there is also activation of transcription factors that leads to increased synthesis of different synaptic proteins that contribute to expand and/or make new synaptic contacts.

Question 43

There are several endogenous mechanisms that may inhibit pain signalling. Describe different mechanisms for inhibitory pain modulation

(1) at the segmental level (in the spinal cord and in the trigeminal system),
(2) via descending systems and
(3) in the brain. Include the CNS regions, and transmitter substances involved, in your answer. (7p)

Answer 43

1) At the segmental level: “Gate control” Activation of Aβ-fibres (sensitive to touch, vibration etc) may inhibit the transmission of pain signals at the first synapse in the dorsal horn of spinal cord, possibly via activation of inhibitory interneurons releasing enkephalins or GABA etc).
2) Descending systems: The Periaqueductal Gray (PAG) projects down to the Raphe Nuclei (containing serotonin neurons) in the medulla and to the locus coeruleus (LC, containing noradrenaline-neurons) which in turn project to the dorsal horn. Serotonin and noradrenaline are able to inhibit nociceptive signalling in the dorsal horn, either directly or via activation of inhibitory interneurons releasing enkephalins or GABA etc.
3) Brain regions that are important for pain modulation (both facilitating and inhibitory), especially in chronic pain, include the Anterior Cingulate Cortex (ACC), Insula (In), Prefrontal cortex (PFC) and the Nucleus Accumbens (NAC). Opioid peptides and Dopamine are important transmitter substances involved in these mechanisms.

Question 44

The structure of the retina in the fovea centralis differs from the periphery.

a) Describe three characteristics of the fovea. (3p)
b) Describe the neuroanatomic coupling that regulates how both eyes’ pupils can be affected after light stimulation of one eye. (4p)

Answer 44

a) (1) There are only cones in fovea centralis and (2) they are connected 1: 1 to the ganglion cells. (3) It is a region of high visual acuity.
b) The circuitry responsible for the pupillary light reflex includes projections from the retina to the pretectum and then bilateral projections to the Edinger-Westphal nucleus. Neurons in the Edinger-Westphal nucleus terminate in the ciliary ganglion that innervates the pupillary constrictor muscles.

Question 45

a) Mark the location of the motor cortex in the picture below, and name the gyrus associated with it. (1p)
b) What blood vessels supply the motor cortex? Draw in the approximate regions of the motor cortex that each vessel supplies. (1p)

c) Which neurons give rise to the cortico-spinal tract? 0.5p
d) In which layer of the motorcortex are they located? (0.5p)
e) What are the histological hallmarks of these cells? (1p)

f) Below you will find 4 statements, mark (with an X) if the statement is correct or not. A correct answer gives you 0.5 p and an incorrect answer deducts 0.5p. If you do not know, the answers you can mark do not know that gives 0p. The question cannot give a negative score.

1. Putamen is located laterally to the internal capsule
2. The crus cerebri is located in the dorsal mesencephalon
3. Nucleus caudatus is located medial to thalamus
4. The corticospinal tract decussates in the pons

Answer 45

c) Pyramidal neurons
d) Layer V
e) Pyramidal shape and a large cell body, distinct apical and basal dendrites.
f) 1. true 2, false 4 false 5 false

Question 46

A) What are the differences between Parkinson’s and Huntington’s diseases? Explain the differences in terms of the behavioral dysfunction and the network organization of the basal ganglia. (4p)

B) What are common treatments for Parkinson’s disease? (2p)

Answer 46

a) Parkinson’s disease (PD) is caused by degeneration of dopamine cells in the substantia nigra pars compacta whereas in Huntington’s disease (HD) there is damage to cortical and striatal neurons. In PD there is imbalance between the BG direct and indirect pathways in which the direct pathway is weakened in comparison. In HD it is the opposite, the imbalance causes a weakening of the indirect pathway. The symptoms of PD include rigidity, inability to initiate movements, stiffness, and tremor. In HD the effects are of hyperexcitability, hyperkinesia, involuntary movements and tics.
b) Dopamine replacement by L-DOPA. Electrical stimulation (deep brain stimulation).

Question 47

a) Our understanding of the prefrontal cortex (PFC) has increased substantially the last 20 years with brain imaging techniques such as fMRI. Pair the brain areas in the PFC to the following functions: 1) Emotion regulation, 2) Regulation of non-emotional content, 3) Speech production. (3p)
b) Evoluationary pressures that have formed our brains include a need for fast information flow, damage-resistance and a manageable energy consumption. With respect to the connectivity structure of the cortex, specify how it supports ”functional specialization” and ”functional integration”. (2p)
c) PU-relaterad fråga. Du arbetar som läkare. Med utgångspunkt från vad du lärt dig under kursen och PU-dagen, beskriv hur du lägger upp patientsamtalet så att det stödjer dina patienters förmåga att komma ihåg vad som sägs under samtalet och så att de följer din ordination om medicinering. (3p)

Answer 47

a) 1. orbifrontal cortex
2. dorsolateral prefrontal cortex
3. brocas area

b)

Cells with common functional properties are grouped together and form specialized modules in particular brain regions. The connections between cells in specilized modules are short, use less energy and are often highly plastic.

Functional integration is supported by longer connections that go through ”hub regions”. The hub regions are mainly found along a central-axis, and hub regions tend to be characterized by their involvement in many different cortical functions.

The brains functioning is dependent on both functioning of speliazied modules but also on intact long-range connections between hub regions.

Question 48

a) Sleep is an essential phenomon of the brain. With respect to the more general regulation of sleep and wakefulness, describe the role of thalamus for sleep and wakefulness. (2p)
b) What are the acute consequences of sleep deprivation for how the brain will work the next day. (4p)

Answer 48

a) Thalamic neurons have an important role for sleep regulation. During wakefulness, the so called ”relay neurons” are depolarised and function as relay neurons, but when hyperpolarized they start oscillating, which causes the brain to fall asleep. The oscillations cause a synchronization of the cells in the brain resulting in a switch to slower frequencies, such as theta activity, with a higher amplitude, a result of the increased synchronization of neural activity. Without input from the reticular activiation system, the relay-neurons are hyperpolarized by interneurons.

b)

The cognitive deficits include

• Problems to keep up attention across time, particularly causing a variability
• Poorer ability to regulate emotions (can contriobute to worse mood)
• Slower processing speed in the brain
• Poorer plasticity (e.g. worse at encoding declarative memories)
• A poorer consolidation of declarative memories (of what happened yesterday)
• Poorer working memory
• More easily distracted
• Increased hunger

The mechanisms behind deteriorations of cognitive funcfions include an increased pressure for sleep on the local level and a reduction of activity in the arousal systems. This typically results in an increase of the variability of cognitive functions, a poorer connectivity in the brain, particularly connections involving the frontal cortex. Sleep deprivation also results in reduced levels of energy in the brain, a build up of rest products/toxins and a higher synaptic pressure, and it is likely that these alterations contribute to the deterioration of cognitive functions.

Question 49

Ion channels comprise two different types: gated- and non-gated channels. Gated ion channels display the following properties: (2 p)

a) They can only be activated by stimuli acting from the outside of neurons
b) They can be ionotropic receptors
c) They require specific stimuli to be activated
d) They contribute to setting the resting membrane potential of neurons
e) All gated ion channels become inactivated with a prolonged stimulation

Answer 49

b) They can be ionotropic receptors
c) They require specific stimuli to be activated

Question 50

An Action potential (AP) transmits the electrical signals along the axons of neurons. Which of the following statement(s) is(are) correct: (2 p)

a) The electrical signal of an AP is converted to a chemical signal at axon terminals
b) Action potentials are triggered by ligand-gated sodium channels
c) Action potentials unidirectional propagation is controlled by sodium channel inactivation
d) Action potentials are mediated by voltage-gated channels
e) The frequency of action potential firing does not change with the stimulus strength

Answer 50

a) The electrical signal of an AP is converted to a chemical signal at axon terminals
c) Action potentials unidirectional propagation is controlled by sodium channel inactivation
d) Action potentials are mediated by voltage-gated channels

Question 51

The passive membrane properties of neurons determine the efficacy of summation of synaptic inputs. Which of the following statement(s) is(are) correct: (2 p)

a) The time and space constants determine the shape and amplitude of action potentials
b) Synaptic summation is more efficient with higher time and space constants
c) The time and space constants affect the release of transmitters from axon terminals
d) The time and space constants only influence sub-threshold postsynaptic potentials
e) The resting membrane potential does not influence the time and space constants

Answer 51

b) Synaptic summation is more efficient with higher time and space constants
d) The time and space constants only influence sub-threshold postsynaptic potentials

Question 52

All neurons have a resting membrane potential (RMP) around -65 mV. Which of the following statement(s) is(are) correct: (2 p)

a) Only ion flux through gated-ion channels determines the RMP
b) TheRMPissetbyacombinedfluxofNaandKions
c) The permeability of Na vs K does not play an important role in setting the RMP
d) The RMP influences the direction of ion flux through ion channels
e) The RMP can vary between neurons in different regions of the brain

Answer 52

b) TheRMPissetbyacombinedfluxofNaandKions
d) The RMP influences the direction of ion flux through ion channels
e) The RMP can vary between neurons in different regions of the brain

Question 53

a) Poisoning by Botulinum toxin and Tetanus toxin gives rise to different symptoms. How do these toxins act? How do the symptoms produced by the two toxins differ and how can this be explained? (4p)
b) The SNARE proteins synaptobrevin, syntaxin and SNAP25 are critical for neurotransmitter release but they require aditional proteins to mediate their function - describe briefly the roles of complexin and synaptotagmin in the release process (2p)

Answer 53

a) Both toxins act as proteases that specifically cleave SNARE proteins (different subtypes of Botulimun toxin cleave synaptobrevin, SNAP25 and syntaxin, respectively, while Tetanus toxin cleaves synaptobrevin). In doing so they block fusion os synaptic vesicles with the plasma membrane and therby neurotransmitter release from the affected nerve terminal.
Botulinum toxins give rise to a flaccid paralysis (reduced muscle tone) while Tetanus toxin gives rise to muscle spasms (increased muscle tone).
This difference is explained by the fact that Botulinum toxins are taken up into neuromuscular nerve terminals and act directly in the terminal they have been taken up into. In contrast, Tetanus toxin, which is also taken up into neuromuscular nerve terminals, undergo retrograde transport back to the cell body of the motorneuron. Thereafter, the toxin is transported across synapses and is taken up into presynaptic terminals of interneurons, primarily inhibitory interneurons, where they cleave synaptobrevin, to reduce the release of inhibitory neurotransmitters, which causes enhanced activity of the motor neurons.

b)

Complexin acts prior to the fusion process. It binds to the partially formed

SNARE complex to stabilize the complex (to make it ”primed” for release).

2+ 2+
Synaptotagmin binds Ca , and when bound to Ca it replaces complexin, triggers

formation of a complete SNARE complex and thereby triggers fusion of the vesicle with the plasma membrane.

Question 54

There are two main classes of neurotransmitter – small molecule neurotransmitters and neuropeptides (”large”), respectively. Give two examples of each type and describe where they are synthesized and where they are stored – (6p)

Answer 54

Small molecule neurotransmitters: For example glutamate, GABA, glycine acetylcholine, and monoamines like dopamine and serotonin. They are synthesized in nerve terminals and stored in (small) synaptic vesicles (SV) that are aggregated at active zones. The monoamines can additionaly be synthesized in cell bodies and stored in large dense-cored vesicles (LDV)

Neuropeptides: For example enkephalins, endorphins, NPY, substance P, somatostatin, cholecystokinin. They are synthesized in cell bodies and stored in large dense-cored vesicles (LDV) that are located outside of the active zones.

Question 55

For neurological examination of patients with pain, it is important to know about possible mechanisms behind an altered pain sensitivity. The following questions are about different forms of sensitization of pain signalling.

a) Describe the meaning of the term allodynia. (1p)
b) Give example of two different forms of allodynia. (1p)
c) Describe the meaning of the term hyperalgesia. (1p)

d) Describe two different forms of hyperalgesia. What distinguishes them from each other? Where along the pain pathways does the sensitization occur in the two types of hyperalgesia, respectively? (3p)

Answer 55

a) Allodynia = when a normally non-painful stimuli induce pain.¨
b) Two of the following: Cold-allodynia Heat-allodynia

Static mechanical allodynia Dynamic mechanical allodynia

c) Hyperalgesia = when normally painful stimuli are experienced with increased strength.
d) Primary hyperalgesia and secondary hyperalgesia.

Primary hyperalgesia occurs very quickly in the injury area itself – is due to a sensitization of the peripheral nociceptors.

Secondary hyperalgesia occurs in (is localized to) the intact tissue adjacent to the damaged area of the skin – is due to the sensitization of neurons at the spinal level (and probably also supraspinally) – gives increased sensitivity to especially mechanical stimulation.

Question 56

a) The major function of the middle ear is to match low-impedance (low resistance) airborne sounds to the higher-impedance fluid of the inner ear. Most of the energy is reflected when going from low-impedance to high-impedance. However, the middle ear compensates for this loss of energy by two different mechanisms. Name these two processes that result in little loss of energy from the middle ear to the inner ear. (4p)
b) Humans use at least two different strategies to localize sound in the horizontal plane. Describe these two different strategies and name the region of the brain where these two different strategies take place. (4p)

Answer 56

a) The first is the large size difference between the tympanic membrane and the oval window. The second is the mechanical advantage gained by the lever action of the three bones in the middle ear.
b) The lateral superior olive detects the level difference between the two ears while the medial superior olive detects the time difference between the two ears.

Question 57

a) Name the CNS regions shown on the sections (A-D) 2p
b) Explain how the brainstem receives blood and how the vessels are located in relation to the brainstem. 2p
c) Draw a simple picture of the spinal cord and indicate where the descending pathways that control locomotion are located. Also, show what part of the gray matter they control. 2p

Answer 57

a) A- spinal cord (sacral), B mesencephalon, C medulla obolongata, D pons
b) Sufficient with: The vertebral arteries goes along the ventral sides of medulla oblongata. Where medulla transitions into pons, the two vertebral arteries join at the midline to form the basal artery. The basal artery goes along pons and mesencephalon. More detail is appreciated but not required.

c)

Question 58

a) Many of the central motor programs are localized to the brainstem-spinal cord level of the CNS. The concept of motor programs, or central pattern generators, is useful when considering how the brain controls our movements.
Give a definition of a central motor program, and give also two examples located atthe brainstem level. 2p

b) Locomotor movements are controlled by a well-studied central motor program. Indicate where the locomotor program is located, and describe briefly how this was first shown experimentally. 1p
c) Give a brief account of the brainstem mechanisms responsible for the initiation of activity, as well as the level of activity, of the central locomotor program. 3p

Answer 58

a) A central motor program is a network of neurons, interconnected so that when the network is activated, a specific output pattern is generated that drives the proper motoneurons to produce a certain motor pattern (1p).
Two examples: The CPG for respiration, and the CPG for swallowing are both localized to the brainstem (1p). Other examples: CPGs for chewing, eye movements.

b) The central motor program for locomotion in located in the spinal cord (0.5p).
This was shown in experiments on cats, walking on a treadmill belt. After transection of the spinal cord at the lumbar level, i.e. isolating the caudal part of the spinal cord from the rest of the CNS, the hindlimbs (that are innervated from the caudal spinal cord) could still perform well-coordinated rhythmic stepping movements, showing that the CPG for locomotion must be located in the spinal cord (0.5p).

c) Activity of the locomotor CPG in the spinal cord is initiated by excitation from the reticulospinal descending pathway (1p).
The level of activity in the CPG, i.e. the speed of locomotion, is regulated by the frequency of firing in the reticulospinal pathway, - a higher frequency drives the CPG to a higher activity level and faster locomotion (1p).

When locomotion should be initiated, the Mesencephalic Locomotor Region (MLR) will first be activated (through disinhibition from the Basal Ganglia output nuclei (SNr)). The MLR will then in turn activate the reticulospinal pathway (1p).

Question 59

The reward system is very important for guiding us in what we want and to reward us when we carry out differen behaviours. One of the main functions of the reward system is to give different objects, people and behaviours a positive value so that we like them.

a) The Mesolimbic dopamine system is believed to play an important part in the reward system. Which brain regions are part of the mesolimbic dopamine system? Give evidence for this hypothesis. (4p)
b) This hypothesis has been questioned. Which evidence goes against that this system mediates reward? (1p)
c) Which role does the mesolimbic dopamine system play in addiction? (2p)

Answer 59

a) Response: Ventral Tegmental Area (VTA) and nucleus accumbens/ventrala striatum. Evidence: “In principle, all addictive agents increase dopamine levels in this system. - Also natural rewards (like six) activate this system.
- Dopamine neuron that originates from these areas and that projectes to nucleus accumbens is regulating “salience” (motivation and desire), which is important input for choosing between different behaviors.
- Rats learning self-administering drugs stop taking them if you block dopamine receptors at the nucleus accumbens with a D2-receptor antagonist.
b) Response: The pleasure effects of drugs cannot be blocked with dopamine receptor antagonists, and some addictive drugs, e.g. benzodiazepines do not stimulate this system, even stress seems to activate this system. There is also experimental support for the release of dopamine before the reward itself (there are enough cues for things we want) and that opioids are released when the goal is achieved. This suggest that dopamine is involved in wanting (giving a value of what we want) rather than the reward itself.
c) Response: It is important for learning which stimuli that gives reward, i.e. it is central for associating the drug with pleasure. Additionally, the activity of this system increases when a drug dependent person sees something that he / she associates with drug intake, eg cues that are correlated to suction after the drug. This is also called “wanting” and differsfrom”liking”thatcorrespondstothewell-being/rushyougetfromthedrug. In addition, addiction (and addiction) over time often leads to a downregulation of the domination system, which results in the need to increase the dose to get the same rest.

Question 60

a) What central function does anterior cingulum has for when we decide between different behaviours? (1p)
c) What parts of the prefrontal cortex and cingulum are involved in emotion regulation? (1p)
d) What parts of the prefrontal cortex and cingulum are involved in regulation of non- emotional regulation (1p)

Answer 60

a) It keeps track of how much you value different things, i.e. reward anticipation.
c) Orbifrontal PFC/mPFC and anterior/rostral Cingulum
d) Dorsolateral PFC and caudal Cingulum

Question 61

The electrical activity of neurons is generated by ion flow though ion channels. Which of the following statement(s) is (are) correct regarding the ion channels: (2p)

a) Ion channels are membrane lipids that allow ion to pass only in one direction
b) Ion channels allow all ions to pass through
c) Ion channels have a selectivity filter to specifically select the ions that will pass through
d) The flow of ions through channels requires energy in form of ATP
e) The direction of the flux of ion is determined by the driving force

Answer 61

c) Ion channels have a selectivity filter to specifically select the ions that will pass through
e) The direction of the flux of ion is determined by the driving force

Question 62

The resting membrane potential of neurons is around -65 mV and is directly determined by: (2p)

a) Passive flow of ions
b) Gated ion channels
c) Leak K+ and Na+ channels
d) The size of the neuron
e) The neuron’s time and space constants

Answer 62

a) Passive flow of ions
c) Leak K+ and Na+ channels

Question 63

Action potential transmit the electrical signals along the axons of neurons. Which of the following statement(s) is (are) correct: (2p)

a) Action potentials propagate actively from soma to axon terminals with constant amplitude
b) There is an influx of Ca2+ via voltage-gated channels during an action potential
c) The rising phase of an action potential is mediated by Ca2+ influx
d) Action potentials are mediated by non-gated ion channels
e) The slow afterhyperpolarization controls the frequency of action potentials

Answer 63

a) Action potentials propagate actively from soma to axon terminals with constant amplitude
b) There is an influx of Ca2+ via voltage-gated channels during an action potential
e) The slow afterhyperpolarization controls the frequency of action potentials

Question 64

The passive membrane properties of neurons determine the efficacy of summation of synaptic inputs. Which of the following statement(s) is (are) correct: (2p)

a) The time and space constants can vary between different types of neurons
b) The spatial summation increases with an increased space constant
c) The temporal summation decreases with increased space constant
d) Neurons with large time and space constants have less efficient summation
e) The decay time of IPSPs is determined by the neuron’s time constant

Answer 64

b) The spatial summation increases with an increased space constant
d) Neurons with large time and space constants have less efficient summation

Question 65

The abbreviation SNARE stands for ”Soluble NSF-Attachment protein REceptor” which denotes a key group of proteins in the presynaptic terminal. Which are these proteins and where exactly are they localized? How do they function and how do we know that they are of critical importance? (6p)

Answer 65

a) The SNARE proteins synaptobrevin, syntaxin and SNAP25 are critical for neurotransmitter release but they require aditional proteins to mediate their function - describe briefly the roles of complexin and synaptotagmin in the release process (2p)

Answer: Complexin acts prior to the fusion process. It binds to the partially formed

SNARE complex to stabilize the complex (to make it ”primed” for release).

2+ 2+
Synaptotagmin binds Ca , and when bound to Ca it replaces complexin, triggers

formation of a complete SNARE complex and thereby triggers fusion of the vesicle with the plasma membrane.

När aktionspotential når nervände öppnas spänningskänsliga Ca2+-kanaler i den aktiva zonen. Dessa triggar fusion av vesikel med det presynaptiska membranet, varpå transmittorsubstans släpps ut i synaptiska klyftan. Mer detaljerat sker vesikelfusion enligt följande:
• På vesikel sitter ett SNARE-protein, Synaptobrevin (även kallat V-SNARE), samt ytterligare ett protein, Synaptotagmin. På plasmamembranet sitter två SNARE-proteiner: SNAP-25 samt Syntaxin. Dessa kallas gemensamt för T-SNARES.

• Spontant – innan Ca2+-influx – bildar ett antal vesiklar s.k. ”readily releasable pool” genom de tre första stegen i fusionscykeln där proteinet Munc-18 öppnar/rätar ut Syntaxin och bildning av SNARE- komplex påbörjas genom kontakt mellan T- och V-SNARES samt s.k. ”Priming”, där Complexin binder

TRANSMITTORSUBSTANS FRISÄTTNING: Beskriv de principiella stegen vid transmittorfrisättning från en nervterminal. Vad heter mekanismen? Vilka proteiner är involverade i processen? (3p; 2p)

Question 66

a) Glutamate and GABA are the main excitatory and inhibitory neurotransmitter, respectively. They act on a particular class of receptors, called ionotropic receptors, or ligand gated ion channels. Describe the structure of these receptors and the basic principles governing their function (2p).
b) What happens when glutamate binds to its ionotropic receptor (e.g. AMPA or kainate receptor) at resting membrane potential? What ions can flow through the receptor and what generates the excitatory postsynaptic potential (depolarisation) of the target cell? (2p).

The GABAa receptor is the ionotropic receptor for GABA. What are the ions that can flow through this receptor? What happens when a GABAa receptor is activated in parallel to an incoming depolarisation? (2p).

Answer 66

a) vGABA binds to an ionotropic receptor whose activation results in the opening of an intrinsic channel selective for Cl-. When the cell membrane becomes depolarized Cl- will flow through the channel inside the cell (according to their concentration and electrical gradient) thereby repolarizing the membrane and reducing the probability of the generation of an action potential.

b)

AMPA- och kainatreceptorer är icke-selektiva katjonkanaler (permeabla för både Na+ och K+), som aktiveras av glutamat. Vid vilomembranpotentialen (ca -70 – -90 mV) ger bindningen av glutamat till AMPA- eller kainatreceptorer upphov till en inåtgående Na+-ström vilken genererar en EPSP.

NMDA-receptorn är en typ av glutamatbindande receptor som skiljer sig från AMPA- och kainatreceptorer, genom att den även regleras av membranpotentialen (voltage-gated). Denna egenskap beror på bindningen av Mg2+-joner till receptorn, vilket blockerar kanalen vid vilomembranpotentialnivån. Vid depolarisering släpper Mg2+-blockaden och kanalen kan aktiveras, vilket även kräver att glutamat är bundet till receptorn. NMDA-kanalen är även permeabel för Ca2+- joner.

c)

Question 67

Question 1: Explain how the somatosensory cortex is affected by either decreased use of a limb (as in amputation) or increased use of a limb. (3p)

Question 2: Suppose a patient has decreased sensitivity to vibration and pressure in the skin on his/her right side from the umbilical region and downwards. Except for that no other tactile defects are present. Where would you suspect the injury to be located and at what level is the injury/problem? (3p)

Answer 67

Representation ökar i förhållande till användning; minskar vid amputation, men består ofta något vilket förklarar fenomenet med fantomsmärta.

) Primära somatosensoriska cortex hos människan är belägen bakom den centrala fåra som skiljer frontala cortex från parietala cortex. Olika kroppsdelar upptar olika stora delar av cortexytan. Diskutera anledningen till detta. (110329ORD, 2p)

Beroende av vilken finkänslighet som krävs (är relevant) för respektive område, t.ex. fingrar kräver bättre känsel än rygg då vi med fingrar t.ex. känner av och håller i små objekt.

right spinal cord?

Question 68

Describe the anatomical circuitry of the pupillary light reflex and include the cranial nerves involved in this circuitry. (4p)

Explain why light shined in one eye results in the constriction of both pupils. (4p)

Answer 68

The circuitry responsible for the pupillary light reflex includes projections from the retina to the pretectum and then bilateral projections to the Edinger-Westphal nucleus. Neurons in the Edinger-Westphal nucleus terminate in the ciliary ganglion that innervates the pupillary constrictor muscles.

“projections from the retina to the pretectum and bilateral projections to the Edinger- Westphal nucleus. Neurons in the Edinger-Westphal nucleus send bilateral axons via the oculomotor nerve to terminate in the ciliary ganglion that innervates the constrictor muscle in both eyes.”

Question 69

When performing skilled movements, like hand and finger movements, requiring a conscious control, the motor areas of the cerebral cortex are heavily involved.

1. The precise control of independent finger movements in man and other primates is dependent on specific connections between the motor cortex and the spinal cord. Describe these connections, and give an explanation why such connections are required for this type of skilled movements. (2p)
2. Different aspects of planning have to be carried out before a skilled movement can be successfully performed. Describe this movement planning – which cortical areas that are involved, and the strategies being utilized. Mention also how these movement planning strategies have been revealed experimentally. (6p)

Answer 69

Frontala delar av hjärnbarken (t.ex prefrontalcortex) är viktiga för att planera rörelse. Härifrån skickas impulser till premotorområden som premotorarean (PMA), supplementära motorarean (SMA) och posteriora parietalcortex. Här omsätts den planerade handlingen i motorprogram. Cellerna på denna nivå kodar inte direkt för kontraktion av en viss del av en muskel utan kan aktiveras exempelvis innan en rörelse oavsett vilken hand som utför den eller vem som utför den (spegelneuroner) eller innan en viss rörelsesekvens. Dessa områden skickar vidare informationen till primära motorbarken som i sin tur direkt kontaktar motorneuron i ryggmärgens framhorns laterala del (laterala corticospinala banan). Denna bana är korsad och står för den finmotoriska delen av rörelsen. Premotorområden och primära motorcortex kontaktar även nervceller i hjärnstammens formatio retikularis som i sin tur projicerar till ryggmärgens framhorn (den reticulospinala banan) där de (oftast via interneuron) kontaktar motorneuroner. Denna bana ser till exempel till att man inte ramlar omkull på grund av tyngdpunktsförändringen då vi sträcker ut handen. Den styr även annan grovmotorik – framförallt i proximal muskulatur och är till viss del dubbelsidig.

Question 70

Use the picture below and explain where the regions you wrote about in the previous questions are located and how the descending cortical signal reaches the motor neurons in the spinal cord. Also name the involved anatomical structures. (4p)

Answer 70

Question 71

Emotions are important to motivate the decisions and behaviours that people chose to engage in, in different situations. For example, emotions are essential to protect us from a wide range of threats, such as physical threats (e.g. snakes), psychological stress (e.g. shame), social threats (e.g. social exclusion), etc. Rightfully, the involved neural circuits are often called “survival circuits”. In addition, our ability to detect and analyse other people’s emotions is essential to understand their intentions and for successful social interactions. Disturbances in emotional control can be related to phobias, post-traumatic stress disorder (PTSD), panic attacks and schizophrenia.

a) Name the three components necessary for an emotion (3p)
b) Name the structure central for producing emotions as well as involved in detecting and learning about aspects in the surrounding with emotional significance. (1p)
c) Name the structure responsible for down regulation the strength of an emotion (1p)
d) Name and describe an additional neural structure central for emotions (you are free to chose any relevant structure as long as you can accurately motivate why). (2p)

Answer 71

a)

b)

c)

d)