After Midterm Flashcards
(299 cards)
1
Q
What is coincidence detection?
A
Temporal conjunction of neural activity leading to changes in synaptic strength.
2
Q
What happens when an aversive stimulus to the tail (UCS) is paired with the activation of the siphon sensory neuron (CS)?
A
Increased gill withdrawal to a touch of the siphon in the absence of the aversive stimulus.
3
Q
How is classical conditioning different from sensitization?
A
It required fewer repetitions to produce a big withdrawal and it showed specificity for siphon touch (the paired stimulus).
4
Q
In classical conditioning of the Aplysia gill withdrawal reflex, what is the signal that temporally links activity of different neurons?
A
Calcium
5
Q
What does calmodulin do?
A
Increases the activity of adenylyl cyclase
6
Q
How does amplification occur in the Aplysia gill withdrawal reflex?
A
When the touch and the shock are close together
7
Q
What do PKA catalytic subunits do?
A
Phosphorylate K channels leading to less hyperpolarization and broader action potentials due to increased calcium influx.
8
Q
What causes short-term behavioral facilitation?
A
Post-translational changes (phosphorylation) of a protein (K channel) leading to increased release from the sensory nerve terminal.
9
Q
What is the probability of vesicle release (p) very sensitive to?
A
Intracellular Ca
10
Q
What are k, n and p?
A
k = size of quantum
n = number of vesicles that could potentially release
p = probability of any vesicle releasing
11
Q
What is the overall likelihood of a vesicle being released equal to?
A
P* = n x p
12
Q
What happens if the time between the shock and the touch is too long?
A
There will still be sensitization, but no amplification
13
Q
How does the progression from short-term to long-term sensitization occur?
A
Sustained PKA activation from repeated shocks eventually phosphorylates CREB, which activated CREs that regulate DNA to increase transcription to make proteins.
14
Q
How is ubiquitin hydroxylase made?
A
The result of CREB mediated gene expression/regulation
15
Q
Why does specificity occur in classical conditioning?
A
Non-stimulated sensory neurons (ex. mantel) doesn’t have an increase in Ca concentration in its presynaptic terminal.
16
Q
Why is the order of the US (shock) and CS (touch) important?
A
Ca needs to rise before 5HT is release so Ca-calmodulin can prime the AC so the the GP will have a greater effect
17
Q
For conditioning, should the US (shock) or the CS (touch) be first?
A
The touch should come before the shock. If the shock comes first, there will be some sensitization, but no conditioning.
18
Q
What is Hebbian plasticity?
A
Correlated presynaptic and postsynaptic activity produces long-term enhancement of connections (neurons that fire together wire together)
19
Q
Where are long-lasting changes in synaptic efficacy often studied?
A
Hippocampus - CA3 to CA1 synapses
20
Q
What is channel is required to induce LTP at CA3-CA1 synapses?
A
NMDA-R activation (voltage dependent)
21
Q
Why does the siphon touch cause a bigger siphon withdrawal than the mantle touch?
A
There is amplification of adenylyl cyclase activity by Ca-calmodulin because it is paired with the shock.
22
Q
Is the mantle touch or the siphon touch paired with the tail shock?
A
Siphon touch
23
Q
What blocks LTP at the CA3-CA1 synapses?
A
Fast Ca chelators
24
Q
What is long term depression?
A
Postsynaptic reduction in sensitivity not equal to “synaptic depression”
25
Why is it important that long-term plasticity is dual directional?
To avoid all synapses becoming super strong. LTP can erase LTD and LTD can erase LTD.
26
What is activated with lower levels of calcium?
phosphatases
27
How do NMDA receptors currents mediate LTP and LTD?
Large/fast Ca increase = LTP
Small/slow Ca increases = LTD
28
What are coincidence detectors?
Two "events" that occur close together in time cause persistent changes in behavioral responses at later times.
29
What cells synapse onto each other in the CA1/CA3 synapse of the hippocampus?
Cell from perforant path (entorhinal cortex) synapses onto a granule cell that synapses onto CA3 pyramidal cell that synapses onto CA1 pyramidal cell.
30
What would happen to the post synaptic potential if the presynaptic cell was stimulates with a train of stimuli?
Facilitation and temporal summation would occur until the there is a period of diminished response due to transmitter depletion.
31
What is the signal mechanism/pathway underlying LTP at the CA3 CA1 synapse?
Activation of the postsynaptic NMDA receptors allow the influx of Ca and Na, causing substrate phosphorylate and the insertion of additional AMPA receptors.
32
What two kinases are activated by NMDA receptor activation in the CA1 postsynaptic pyramidal cell?
Ca/Calmodulin Kinase II and PKC
33
What causes an increase in postsynaptic response to glutamate?
Depolarization of the postsynaptic cell while applying glutamate.
34
What is the difference between silent synapses and functional synapses?
Silent - NMDA receptors only
Functional - AMPA and NMDA receptors
35
What features cause the posttranslational changes in existing proteins and long lasting phases that require gene expression?
An early transient phase that relies on protein kinases.
36
Does tetanus have high or low levels of kinase activity?
high
37
What recruits AMPA receptors into the dendritic spines?
Depolarization and glutamate
38
Is CA3/CA1 Hebbian? Why?
CA3/CA1 is Hebbian because its activity needs to be both presynaptic and postsynaptic.
39
What happens to active zones in LTP?
They form a horseshoe shape, allowing for "two" active zones - doubling the probability of an event.
40
What happens if the Schaffer collaterals are only stimulated two or three times per minute?
The size of the evoked EPSP in CA1 remains constant
41
What happens if the Schaffer collaterals are given a brief, high-frequency train of stimuli?
LTP - long lasting increases in EPSP amplitude
42
What causes an increase in the EPSP in CA1?
Pairing of a stimulus with depolarization of CA1 and close timing between paired pre/postsynaptic activity.
43
How is LTP input specific?
It is restricted to ACTIVATED synapses rather than to all the synapses on a given cell.
44
What leads to short-term sensitization vs long-term sensitization?
Short - post translational changes
Long - change in gene expression
45
Why can the synthesis of new proteins occur in the dendrites?
Ribosomes are present
46
If new synapses or new active zones are increased by LTP, is k, n or p increased?
47
How can LTP be increased/decreased?
Increased - faster, close together stimuli
Decreased - slower, spaced out stimuli
48
Why do small, slow NMDA-mediated Ca current increases lead to LTD?
Low concentrations of Ca can only activate phosphatases, not kinases.
49
What is spike timing dependent plasticity (STDP)?
The order and precise temporal interval between presynaptic and postsynaptic spikes determine the sign and magnitude of LTP or LTD.
50
How does spike timing dependent plasticity lead to LTP and LTD?
LTP - presynaptic spike, then postsynaptic spike (pairing enhances)
LTD - postsynaptic spike, then presynaptic spike (antiparallel depresses)
51
How does long-term synaptic depression occur in the cerebellum?
Climbing fiber and parallel fibers of granule cell axons excite the inhibitory Purkinje fibers
52
Is LTD in the cerebellum Hebbian or non-Hebbian?
Hebbian - presynaptic and postsynaptic activity (coincident detection)
53
What is the role of the climbing fiber in LTD in the cerebellum?
Depolarizes the dendritic spine of the Purkinje cell through a voltage-gated Ca channel.
54
What does it mean for a receptor to be polymodal?
Naturally sensitive to more than one stimulus modality.
55
What is the threshold detection of a stimulus?
The weakest stimulus that produces a response in a receptor 50% of the time.
56
How does the size of dynamic range influence sensory discrimination?
Large dynamic range means poor sensory discrimination and small dynamic range means high sensory discrimination.
57
What is range fractionation?
Groups of receptors can work together to increase dynamic range without decreasing sensory discrimination.
58
What is the dynamic range of a receptor?
The range of stimulus intensities over which a receptor neuron can encode changes in intensity as changes in neuronal activity (between threshold intensity and receptor saturation)
59
What is dynamic range dependent on?
Firing rate and depolarization - can't encode when saturated or if the stimulus isn't strong enough.
60
How do sensory neurons code stimulus intensities?
Through changes in action potential frequency or through graded membrane potential change (depolarization).
61
Stevens's Power Law
Measures the relationship between physical stimulus intensity and the perceived intensity of the physical sensory stimulus.
62
What is phasic firing rate?
Produce APs only at the beginning or end of the stimulus
63
How is tonic non-adapting firing different from tonic slowly adapting firing?
Non-adapting - produce APs without much slowing down as long as the stimulus continues
---IIIIIIIIIIIIIIIIIIIIIIII---
Slowly adapting - AP frequency decreases if stimulus intensity is maintains at the same level
---IIIII III II II II II I I I---
64
Why are action potentials produced at the end of a stimulus?
Release of suppression
65
What causes shifts in dynamic range?
Adaptation - depolarization changes
66
Which afferent fibers project to the medulla ipsilaterally/contralaterally?
Ipsilaterally - Mechanoreceptors (touch) - (then crosses at medulla)
Contralateral - Nociceptors (pain/temperature)
67
Which cells are slowly adapting and which are rapidly adapting?
Slowly - Merkel and Ruffini
Rapidly - Pacinian and Meissner
68
What is Piezo 2?
A mechanotransducer for touch, proprioception and interception
69
What is unique about Pacinian Corpuscle afferent fiber endings?
Can be free or encapsulated as part of an organ
70
What two things does sensory adaptation depend on?
Properties of ion channels in the sensory neuron or the physical properties of the sensory "organ" in which the receptor is found.
71
What are the four mechanoreceptors and their functions?
Merkel - form/texture/edges
Meissner - motion and grip
Pacinian - vibration and pressure
Ruffini - stretch and proprioception
72
Which mechanoreceptor encodes the position of Braille most accurately?
Merkel
73
Which mechanoreceptor response take a while to turn on and off?
Pacinian
74
What is the importance of spatial resolution?
Important for the cortex to distinguish two points in space
75
What are dermatomes?
Body surface mapped to segments of spinal cord
76
What are the two somatosensory tracts synapse at the caudal medulla and what are their functions?
Gracile - lower body
Cuneate - upper body
77
What sensory stimuli is not relayed to the thalamus?
Olfaction
78
Where does mechanoreceptor inputs decussate?
Medulla
79
In what layer of the cortex does the majority of thalamic input terminate?
Layer 4
80
What is the function of the medial lemniscus pathway?
Transport sensory spinothalamic information from the caudal medulla to the ventral posterior lateral nucleus of the thalamus.
81
What is the pathway for mechanoreceptors coming from the face?
Trigeminal complex - trigeminal ganglion enters into the brainstem so the pathway crosses over immediately
82
What is pathway for proprioception?
Spinocerebellar tract - travels ipsilaterally to the cerebellum and synapses in the cerebellum/dorsal column nuclei
83
What proprioceptors provide information on muscle length/tension?
Length - muscle spindles
Tension - Golgi tendon organ
84
What causes the stretch/no stretch in the intrafusal and extrafusal muscle fibers?
Whether the muscle is contracted or relaxed
85
What are the largest and fastest conducting somatosensory axons for?
Proprioception
86
What are the different afferent axon types for the different somatosensory receptor types?
Muscle spindles - Ia/II
Touch - Aβ
Nociception/Temp - Aδ
Nociception/Temp/Itch - C
87
How is the somatosensory cortex organized?
Lateral to medial = up and down the body
Rostral to caudal = homunculus
88
What are the functions of the 4 Brodmann's areas of the somatosensory cortex?
1 - cutaneous (texture)
2 - tactile and proprioceptors (size and shape)
3a - proprioceptors
3b - cutaneous (tactile)
89
What area of the thalamus is important in the somatosensory pathways?
ventral posterior complex
90
What are the two functions of the anterior lateral system?
| two questions
1. Where is the stimulus coming from? (ventral posterior nucleus to S1 and S2)
2. Is the stimulus unpleasant/painful? (midline thalamic nuclei to anterior cingulate/insula)
91
Where does nociceptive and mechanoreceptive projections cross over?
Nociceptive - spinal cord
Mechanoreceptive - medulla
92
What happens to touch and pain perception with a lesion in the spinal cord?
Lose ipsilateral touch and contralateral pain
93
What is the difference between visceral pain and neuropathic pain?
Visceral - mechanical or chemical activation of nociceptors by compression/obstruction in an internal organ that manifests as pain on the body surface
Neuropathic - damage to afferent fibers or central nervous system pathways
94
What are vanilloid receptor VR-1 activated by?
Heat > 45 degrees or tissue injury (capsaicin - from chiles)
95
What do endovanilloids activate?
Transient receptor potential (TRP) channels
96
What is special about TRPM VR1 in birds?
Not sensitive to capsaicin (chile)
97
How does the raphe nuclei inhibit pain?
Serotonin binds to enkephalin neurons (opioid receptors) inhibiting calcium influx in the terminal of the nociceptors
98
How do descending inputs from the locus coeruleus inhibit pain?
Inhibits dorsal horn projection neuron directly or inhibits calcium influx from C fiber (nociceptor)
99
Where does processing of painful stimuli occur?
In the dorsal horn of the spinal cord
100
What happens to pain perception when a mechanoreceptor and a nociceptor are activated at the same time?
Inhibitory local circuit neurons are activated, decrease the effectiveness of the C fiber (nociceptor), inhibiting the dorsal projection neuron, reducing pain stimulus
101
What happens with stimulation of the midbrain periaqueductal gray (PAG)?
Analgesic effects - lessens pain reception
102
What blocks PAG analgesic effects?
CB1 blockers
103
What is released from the locus coeruleus?
Norepinephrine
104
What system does the dorsal horn of the spinal cord project to?
Anterolateral system
105
Which somatosensory receptors are unmyelinated?
C fibers (nociceptor)
106
What is hyperalgesia?
A form of peripheral sensitization with increased sensitivity to pain (ex. with sunburn)
107
What is allodynia?
When pain is induced by a normally not harmful stimulus (ex. with sunburn)
108
What substances cause inflammation in response to tissue damage?
Prostaglandins, bradykinins, serotonin and histamine (and ATP and H)
109
Other than the ventral posterior nucleus and the midline thalamic nuclei, where does the anterolateral system project to?
Amygdala, hypothalamus, periaqueductal grey, superior colliculus and reticular formation
110
Why does neuropathic pain often arise following amputation of an extremity?
Due to rewiring of circuits in the absence of sensory input from the amputated limb
111
How does the conduction speed of sound differ in water compared to air?
5 times faster in water than air (air = 340m/s and water = 1500m/s)
112
What part of the ear increases the amount of pressure delivered to the oval window?
ossicles - malleus, incus and stapes (after pressure wave is concentrated on the tympanic membrane)
113
Where in the ear are pressure waves concentrated?
TYMPANIC membrane ("ear drum")
114
What muscles regulates the transmission of sound to the inner ear?
small muscles - tensor tympani and stapedius - that control the tension of the bone joints
115
What is special about a cricket's hearing?
Have a membrane in their foreleg that picks up pressure waves - has a blocking system so the it's auditory system is shut off when it plays its song
116
What are the functions of inner hair cells vs outer hair cells?
Inner - communicate sound information to the brain
Outer - amplify sound vibration, increasing sensitivity to sound
117
What is the Scala media?
The cavity in the cochlea that divides the Scala TYMPANI and the Scala vestibuli
118
What is the function of the TECTORIAL membrane?
Sits on top of the hair cells and move them back a forth
119
What is the difference between the oval window and the round window?
Sound vibrations go in through the oval window and out through the round window
120
What is the function of the basilar membrane?
Sits underneath the hair cells
121
Where are the inner/outer hair cells, tectorial membrane and basilar membrane located?
Scala media
122
What are the different areas of the basilar membrane "tuned" for?
Base - high frequencies
Apex - low frequencies
123
How do cochlear implants work?
They bypass the hair cells by electrically stimulating the afferent
124
What is lateral inhibition?
Ability of excited neurons to inhibit the activity of neighboring neurons, preventing later spread of neuronal activity
125
How are movements of the cochlea converted to neural activity in the brain?
Cochlear movement causes voltage change in hair cells (K flows into tips of hair cells)
126
What is the functions of vestibular hair cells?
Sensory receptors in the inner ear that detect head motion to help with motion coordination
127
What are hair bundles composed of?
Actin-based stereocilia arranged in a staircase-like array
128
What happens when hair cells are depolarized?
Ca influx through voltage-gated Ca channels, causing transmitter release into the auditory nerve endings
129
What happens when hair cells are deflected?
There is a change in membrane potential due to the influx of K causing depolarization of the hair cell, activating Ca channels that trigger transmitter release from vesicles into afferent nerve.
130
How is the INFLUX of K in the hair cells possible?
The fluid in the Scala media has high concentrations of K
131
Approximetaly how many active zones are there in a hair cell?
20 all in close proximity to Ca channels
132
What is the function of spiral ganglion (secondary sensory cells)?
Carry information about auditory stimulus from the inner hair cells to the auditory nerve.
133
What is endolymph vs perilymph?
Endolymph - fluid in the Scala media
Perilymph - fluid in the Scala vestibuli and Scala tympani
134
What is the function of the stria vascularis?
Maintains the ionic composition of the endolymph (amount of K in the Scala media)
135
What is the function efferent modulation in hair cells?
Directly controls the synaptic output of the hair cells
136
How do efferent fibers synapse differently in inner hair cells compared to outer hair cells to modulate activity?
Inner - synapse onto afferent fiber
Outer - synapse onto hair cell
137
Why do outer hair cells only need one afferent fiber?
Need one to signal to the CNS that they are active but don't need more because they are not sound detectors and don't need to transfer sound signals (inner hair cells do this)
138
What is prestin?
A transmembrane motor protein that shortens in response to depolarization, leading to the electromotility of OUTER hair cells
139
What is the importance of the superior olivary complex?
The first place where information from bother ears interacts and is the initial site where spatial locations of sounds is primarily processed
140
What is unique about the projections from the ear?
They are bilateral (ipsilateral and contralateral) - cross over in the brainstem (mid-pons)
141
What is the significance of the inferior colliculus in the auditory system?
It is the first place where auditory information interacts with the motor system - auditory space map
142
What is the function of the medial superior olive (MSO)?
Helps regulates sensitivity of OUTER hair cells through medial efferent system
143
How do short (high frequency) wavelengths vs long (low frequency) wavelengths interact with solid objects?
Short - shadowed/interfered with
Long - bend around the object/harder to interfere with
144
How does the medial superior olive (MSO) compute the location of a sound?
Synaptic potentials from the left and right ears summate to bring MSO cells to threshold
145
What is the function of the medial nucleus of the trapezoid body (MNTB)?
Part of the superior olivary complex that transforms excitatory input from the cochlear nucleus into a widespread inhibitory output (for lateral inhibition)
146
How do lateral superior olive neurons encode sound location using lateral inhibition?
Crossed inhibition - the side that is activated first/more inhibits the activation of the other side using the medial nucleus of the trapezoid body (MNTB)
147
Are vestibular hair cells sensitive to low or high frequencies?
Low
147
What happens in vestibular hair cells when Ca is increased vs decreased?
Increased Ca - slippage of the myosin on the actin filament (closing channels)
Decreased Ca - tension restored in the spring (reopening channels)
147
What is the difference between upper motor neurons and lower motor neurons (alpha motor neurons)?
Upper - originate in the cerebral cortex and travel down to the brainstem or spinal cord where they synapse with local circuit neurons (and sometimes (LMNs)
Lower - begin in the spinal cord and go on to innervate muscles and glands
147
How is the spinal cord organized (for motor/sensory)?
Dorsal horn - sensory
Ventral horn - motor
148
How is the dorsal horn organized?
Midline = proximal motor neurons
Lateral = distal motor neurons
149
Why are there upper motor neurons in the superior colliculus?
Initiate orientating movements of the head and eyes.
150
What are the function of the upper motor neurons in the brainstem?
Postural changes through bilateral projections
151
What is the function of local circuit neurons?
Innervate the lower motor neurons after receiving information from the upper motor neurons and sensory input.
152
What are the differences in function between the motor cortex and the pre-motor cortex?
MC - planning initiation of movement
PMC - create movement
153
What is the difference between a motor pool and a motor unit?
Pool - all motor neurons that go to a particular muscle
Unit - all the muscle fibers innervated by a single motor neuron
154
What is contractile strength of a muscle dependent on?
The firing rate of motor neurons (summation) and the recruitment of additional motor neurons
155
What are the key features of slow motor units?
- Small motor neurons
- Innervate few fibers
- Lots of mitochondria/myoglobin/capillaries
156
How does the location of local circuit neurons (lateral/medial) affect functionality?
Lateral (short distance/ipsilateral) - fine control of distal extremities
Medial (long distance/contralateral) - posture control
157
What causes muscle reflexes?
Positive feedforward excitation that blocks antagonistic action
158
What are the function of gamma motor neurons?
Maintain length of intrafusal fibers (in the muscle spindles) to maintain tension on sensory afferents so they can remain sensitive to stretch
159
What do sensory afferents do in muscle spindles (1a)?
Stretch receptors that detect "length" of intrafusal fibers
160
What happens when the extrafusal muscles contract and intrafusal fibers become slack?
Small lengthening or shortening from the intrafusal muscle fibers cannot be signaled by the afferents
161
What is the function of the Golgi tendon organ?
Maintains the amount of muscle tension and limits the amount of force generated from a muscle
162
What is the difference between 1a vs 1b afferent fibers?
1a - sensory afferent of the muscle spindle
1b - sensory afferent of the Golgi tendon organ
163
Which sensory afferent fibers are in parallel vs series with the extrafusal muscle fibers?
Golgi tendon afferents are in series and muscle spindle afferents are in parallel
164
What is the significance of sensory afferent fibers being in parallel vs in series after a muscle contraction?
Parallel (muscle spindle) - decrease firing/slack
Series (Golgi tendon) - increase firing/tension
165
How does the Golgi tendon organ participate in negative feedback?
1b afferents inhibit the same muscles that create tension via inhibitory interneurons and excitation of antagonistic muscles
166
What is muscle "tone" a result of?
The resting level of firing of alpha/lower motor neurons
167
What is the difference between hypertonia and hypotonia?
Hypo - damage to LMN or spindle afferents
Hyper - damage to UMN or spinal cord
168
Where does the corticospinal tract decussate?
Caudal medulla
168
What are the areas of the brainstem the control chew/swallow, face and tongue
Chew/swallow - trigeminal motor nucleus (middle pons)
Face - facial motor nucleus (middle pons)
Tongue - hypoglossal nucleus (middle medulla)
169
What is the function of the layer 5 neurons of the somatosensory cortex what are part of the corticospinal tract?
Proprioceptive modulation of motor circuits
170
Approximately what percentage of the corticospinal tract crosses over at the medulla to form the lateral tract?
90%
171
What are Betz neurons?
Make up 5% of neurons in the primary motor cortex - synapse directly onto lower motor neurons - important for movement in distal extremities (fingers)
172
Projection from what other area controls facial movements (other than M1)?
Cingulate cortex
173
How is the cingulate cortex able to retain forehead (superior facial) motor control in a common stroke (MCA lesion)?
It is supplied by the anterior cerebral artery and has bilateral projections
174
What happens with damage to the facial nerve?
Lower motor neuron lesion = weakness of superior and inferior facial muscles
175
What are the influences of a single cortical upper motor neuron on muscle activity?
One UMN activates more than one muscle - different patterns of activity depending on what group of UMN are activated
176
What are the main functions of the basal ganglia?
Suppresses unwanted movements, prepares UMN circuits for movement initiation, help pre-motor cortex filter/refine the choosing of the program before going to the primary motor cortex
177
What are the different parts of the basal ganglia?
Caudate
Putamen
Globus Pallidus (internal/external)
Substantia Nigra (compacta/reticulata)
178
What is the difference between the SNpc and SNpr?
SNpc = dopaminergic
SNpr = GABAergic
179
Where is the main input to the primary motor cortex coming from?
Ventroanterior and ventrolateral thalamus
180
What is the function of medium spiny neurons?
receive inputs from the cortex/SNpc/striatum and project INHIBITORY signals to the GP/SNpr
181
Are Globus Pallidus and Substantia Nigra pars reticulata neurons inhibitory or excitatory.
Inhibitory
182
Where does the SNpr project to?
The superior colliculus to control eye movement
183
Why does the caudate/putamen project to non-motor areas (ex. visual/temporal/association)?
Motor functioning is associated with sensory stimuli
184
What happens with inhibition to the substantia nigra pars reticulata?
Disinhibition of the superior colliculus
185
What is the difference of outcome between the direct and indirect basal ganglia pathways?
Direct - excitation of the frontal cortex, promoting movement
Indirect - inhibition of the frontal cortex, decreasing unwanted movements
186
What are the effects of the indirect vs direct basal ganglia pathways on the Globus Pallidus internal?
Direct - decreases inhibitory effects of GPi
Indirect - increases inhibitory effects of GPi
187
What is the significance of the two types of DA receptors in the basal ganglia pathways?
D1 - direct pathway = excitation
D2 - indirect pathway = inhibition
188
What are the effects of D1/D2 on the adenylyl cyclase functioning?
D1 - stimulates production of cAMP
D2 - inhibits production of cAMP
189
What causes Parkinson's vs Huntington's?
Parkinson's = degeneration of dopaminergic neurons in the SNpc
Huntington's = degeneration of neurons in the caudate (a bit in putamen)
190
What is the result of Parkinson's and Huntington's?
Parkinson's = decreased excitation of the motor cortex
Huntington's = increased excitation of the motor cortex
191
What is the pathway for the production of dopamine?
Tyrosine - (tyrosine hydroxylase) - Dihydroxy phenylalanine - (DOPA decarboxylase) - dopamine
192
What is the function of Carbidopa?
Inhibits breakdown of DOPA to dopamine - increases DOPA available to brain
193
What are two enzymes that are known to break down dopamine?
Catechol-o-methyltransferase (COMT) and monoamine oxidase (MAO)
194
What happens if a GABA agonist is injected into the SNpr
Produces involuntary eye movements, resembling hyperkinesia
195
What eliminates the effects of dopaminergic input to the striatum on reward?
D1 antagonists because D1 excites the striatum
196
Does activation of the medial SNpc increase appetitive or aversive conditioning?
Medial = appetitive
Lateral = aversive
197
What did Duchenne discover about the muscles in the face used to smile?
There are muscles around the eyes that are not easily controlled voluntarily (ex. obicularis oculi) that can be stimulated to produce a smile
198
What are the functions of pyramidal and extra pyramidal neurons in facial expressions?
Pyramidal - voluntary muscle contraction control
Extra pyramidal - involuntary muscle contraction control
199
What is the difference between somatic and visceral motor divisions?
Somatic - signals to skeletal muscles
Visceral - signals to glands and cardiac/smooth muscles (ANS)
200
What is the function of the mediodorsal nucleus of the thalamus?
Part of the limbic system that relays emotional meaning/state information to the cortex
201
What is the function of the hippocampus in the limbic system?
Plays a role in the formation of emotional memories but not emotional expression
202
What is the difference between the dorsal and ventral basal ganglia?
Dorsal = striatum (caudate and putamen)
Ventral = nucleus accumbens
203
What is the difference between the lateral and medial amygdala?
Lateral - receives inputs from visual, auditory and somatosensory (pain)
Medial - olfactory system
204
What is the function of the prefrontal and temporal cortical areas in emotion?
Emotional significance of stimuli and emotional learning
205
Describe the lateralization of the amygdala.
Left - reward and differentiating fearful eye shifts from gaze shifts
Right - processing pain and changes in response to pain
206
What are the steps of conditioned fear response to auditory stimuli?
Auditory pathway to medial geniculate nucleus to amygdala = freezing and increased blood pressure
207
What is unique about emotional learning?
It bypasses the sensory parts of the cortex
208
What is the importance of NMDA-R in the amygdala?
LTP and fear conditioning is dependent on NMDA receptors
209
What happens in the amygdala when a neutral stimulus is associated with an aversive or appetitive stimulus?
Response of the neutral stimulus will change
210
What is the function of the orbital and medial prefrontal cortex?
Implicit motor actions and explicit conscious processing to obtain rewards
211
What is the amygdala important for?
Experiencing emotions and recognizing emotions in others
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What is associated with increased blood flow in limbic system structures?
Clinical depression
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What is the organization of the limbic loop through the basal ganglia?
Amygdala/hippocampus/orbitofrontal/anterior cingulate/temporal cortex --> ventral tegmental area --> ventral striatum (nucleus accumbens) --> ventral pallidum/SNpr --> mediodorsal nucleus
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Where are medium spiny neurons located in the basal ganglia?
Project from striatum to the GP and SNpr
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What causes the dopaminergic modulation of the nucleus accumbens (in limbic loop)?
Projections from the ventral tegmentum
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What are the effects of cocaine?
Increase dopamine receptors and block serotonin and norepinephrine reuptake
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What happens in the nucleus accumbens with persistent high levels of dopamine?
Decrease in D2 receptors in the nucleus accumbens
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What are the effects of different drugs on dopamine projections from the ventral tegmental area to the nucleus accumbens?
Opiate – reduce activation of nucleus accumbens
Alcohol – act on dopamine
Barbiturates – regulate dopamine output
Cocaine/Amphetamine - regulate the amount of dopamine being released (presynaptic effects)
Cannabinoids/PCP/opiates - act on the nucleus accumbens
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What happens to the VTA and NA in addiction?
VTA – increase in the tyrosine hydroxylate expression to compensate for the dysfunctional receptors (from dampened response)
NA – transcription of genes is altered (reset what the neuron thinks the normal levels should be at)
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What are the effects of toxoplasmosis gondi (parasitic organism)?
Alters the behavior of mice and rats
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What are the effects of a 6-OH lesion of dopaminergic terminals in the nucleus accumbens?
Attenuation of nicotine self-administration
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What are the main projections in the mesolimbic pathway?
Dopaminergic neurons (VTA) project to the nucleus accumbens, prefrontal cortex, olfactory tubercle, amygdala and septal region
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In the indirect basal ganglia pathway, what is D2 modulation of medium spiny neurons modulated by?
nAChRs
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How does nicotine suppress unwanted movement through the D2 pathway?
Enhances dopamine release to MSN and to glutamatergic pyramidal neurons (that synapse onto MSN). Both MSN and pyramidal have D2Rs.
225
Where does binding of ACh occur in a nAChR?
Between alpha subunit and the adjacent subunit
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What does Bungartoxin do?
Block muscle nAChRs and alpha7 homomeric receptors
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What is an example of a high affinity target of nAChRs?
Epibatidine
228
What are some characteristics of nicotine?
Ionotropic
Soluble
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In what pathway was the largest increase in alpha4YFP fluorescence with nicotine found?
Perforant pathway
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What is the function of the perforant pathways?
Arises from the entorhinal cortex of the parahippocampal gyrus and is the principle source of cortical input to the hippocampal formation. It is strongly upregulated by ACh.
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What happens to alpha4 receptors with chronic nicotine?
Increase in GABAergic but not in dopaminergic. Shift in distribution of intensity between GABAergic vs dopaminergic .
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What happens to the basal firing rate of GABAergic neurons with chronic nicotine exposure?
Increase in basal firing rate - fire faster and respond more strongly (causing decrease in dopaminergic activity)
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What happens to the basal firing rate of dopaminergic neurons with chronic nicotine exposure?
Decreases in basal firing rate and response to nicotine
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What is needed for LTP to occur in nAChRs?
Chronic nicotine exposure with acute nicotine exposure.
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What happens to the a4YFP nAChR subunits on dopaminergic vs GABAergic neurons when exposed to chronic nicotine?
Dopamine - no change in density
GABAergic - increased density
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What causes the decrease baseline firing rate of dopaminergic neurons with chronic nicotine exposure?
Due to increased inhibition resulting from the increase in GABAergic baseline firing rate.
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What receptors are responsible for the facilitation induction of LTP when nicotine is present?
Upregulated alpha4 contain receptors in the perforant path
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What is the visual circadian rhythm pathway?
Photosensitive RGC that contain melanopsin - optic nerve - lateral geniculate nucleus - suprachiasmatic nucleus
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How does melanopsin lead to depolarization?
Through GPCR (Gq) signaling and opening of TRP channels
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What is the function of the pineal gland in circadian rhythm?
Synthesizes melatonin
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What is significant about the per genes in drosophila?
When mutated can change the active vs non-active cycles - shortening or lengthening rhythmic cycles
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What is the molecular mechanism that determines the time cycle of circadian rhythm?
Multiple feedback loops involving synthesis of proteins and the diffusion of these proteins into the nucleus for regulation of gene transcription
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What do EEG signals rely on?
Summation of neural currents so amplitudes are large enough to detect.
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What does neural activity look like during sleep?
Synchronized - strong coordination (sleep spindles)
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What are some characteristics of REM sleep?
- increased eye movements
- increased heart rate
- increased respiration
- decreased muscle movement
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What is the function of the dorsal column nuclei?
Carry fine touch and proprioceptive information from the body to the brain
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What causes the reduced response to somatic sensory stimuli during sleep?
Inhibition of the dorsal column nucleus through cholinergic inputs from the brainstem that go to GABAergic corticothalamic neurons
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What causes the paralysis experienced during sleep?
Inhibition of lower motor neurons
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What happens with stimulation to the reticular activating system vs the thalamus?
RAS - change state from sleep to awake
Thalamus - change state from awake to sleep
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What brain system is active during REM sleep?
Limbic system
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What happens in sleep with activation of the raphe nuclei cholinergic nuclei, locus coeruleus (NE) and tuberomammillary nucleus?
Increased activity = awake
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What is the function of the tuberomammillary nucleus in sleep?
Releases histamine that provides wakefulness
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What is the significance of the lateral hypothalamic area in sleep?
It releases orexin that promotes wakefulness
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What are two kinds of inputs from the cortex to the thalamus?
Drivers (10%) and modulators (90%)
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What is the function of the ventrolateral preoptic nucleus in sleep?
Promotes sleep by inhibiting cholinergic and aminergic circuits and tuberomammillary nucleus (TMN) circuits
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What is the function of reticular cells (not part of the RAS)?
Inhibitory (GABAergic) cells in the thalamus
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What leads to the sleep spindle recordings in EEGs?
Series of impulses transmitted by the GABAergic neurons (reticular cells) hyperpolarize the thalamocortical neurons and cause them to generate action potentials that are transmitted to the pyramidal neurons in the cortex.
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How does bursting occur in the thalamus?
1. GABAergic reticular cells hyperpolarize
2. Ih current activated by the hyperpolarization
3. Ih current depolarizes (-35mV)
4. Membrane potential goes from -80mV to -60mV
5. T-channels activated by depolarization
6. Membrane potential brough to -45 = action potentials (Na/K spikes)
7. T-channels inactivated by prolonged depolarization
8. Ih inactivated by by depolarization
9. Inactivation wears off
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Why is the time course of bursting potential important?
Time course to activate T-type Ca channels is similar to the time it takes to replenish NT in the presynaptic terminal
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How are the T-type calcium channel activated/inactivation in thalamic bursting neurons?
Channels activates with even a little depolarization (low threshold) from Ih current and inactivates quickly if the membrane stays depolarized
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How is the inward hyperpolarization current activated/inactivated in bursting neurons?
Ih is slowly activated by hyperpolarization and then inactivates slowly.
261
What two players are needed for bursting to occur in thalamic neurons?
T-channels (ICaT)
Hyperpolarization activated inward current (Ih)
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How is Ih current upmodulated?
By cAMP produced by neuromodulators - don't need as much hyperpolarization to open
Reversal at about -35mV
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What does firing switch from burst to tonic mode?
Reducing hyperpolarization by...
1. modulation of Ih by LC, raphe and TMN (histamine) = more depolarization
2. ACh via muscle AChR to block GABA release from reticular cells
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What are the three modes of neuronal firing for sleep/wake states?
1. Non-busting tonic = relay mode (awake)
2. Rhythm bursting = non-relay mode (sleep)
3. Arrhythmic bursting = "wake up" mode (light sleep)
265
What is the pupillary reflex?
Constricts in the pupil in response to light
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What are the different catecholamines and where are they located in the brain?
Dopamine - substantia nigra and ventral tegmental area
Norepinephrine - locus coeruleus
Epinephrine - medullary epinephrine neurons
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What are the general effects of norepinephrine?
Influences sleep, wakefulness, attention and feeding behavior
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What are the general effects of serotonin?
Regulates sleep, wakefulness and mood (depression/anxiety)
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What are the general effects of histamine?
Mediates arousal, wakefulness vestibular function and attention
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What are the general effects of dopamine?
Involved in motivation, reward and reinforcement
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How are biogenic amines loaded into vesicles?
By vesicular monoamine transporters (VMAT)
using a proton gradient
272
How are the actions of biogenic amines terminated in the cleft?
By re-uptake via transporters (DATs and NETs)
273
What can biogenic amine re-uptake transporters inhibited by?
DA transporter - inhibited by cocaine
DAT/NET - inhibited by amphetamines
274
What are two enzymes that breakdown biogenic amines?
Monoamine oxidase (MOA) and cytoplasmic catechol O-methyltransferase (COMT)
275
What is unique about monoamine vesicles?
Can have a varying amount of transmitter in a vesicle - the amount of monoamines can be regulated
276
How is depression targeted?
1. MAO inhibitors
2. 5HT uptake blockers
3. Tricyclic antidepressants (block reuptake of biogenic amines)
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What is Duloxetine (Cymbalta)?
A 5HT/NE reuptake inhibitor used to treat depression, anxiety, fibromyalgia, nerve pain associated with diabetes and musculoskeletal pain
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What is important to know when weaning off of Duloxetine?
It breaks down rapidly so it is packaged in slow-release tablets, so tablets shouldn't be cut in half - take few pills/lower dosage pills
279
Which family of dopamine receptors activate/inactivate adenylyl cyclase?
D1 - G(as) increase cAMP
D2 - G(ai) decrease cAMP
280
What are the effects of D1 vs D2?
D1 - postsynaptic effects (excitatory)
D2 - presynaptic effects (regulate synthesis/storage of DA) or postsynaptic (alter excitability of target cell)
281
What are the effects of DA receptors found in the arteries?
Vasorelaxive effect
282
What are the effects of DA receptors in the atria of mammals?
Increases contractility and cardiac output without changing heart rate
283
What D4 variant is associated with ADHD?
D4.7 allele
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What is the function of 1st generation antipsychotics (ex. reserpine)?
Blocks uptake of NE into vesicles - decreasing NE release
285
What causes psychiatric disorders?
Altered regulation of biogenic amines
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Why did 1st generation antipsychotics cause depression in normal subjects?
Doesn't target DA but affects DA transporters because NE and DA transporters are similar, so they experience cross agonism
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What do "designed drug" antipsychotics (ex. chlorpromazine/haloperidol) do?
Block D2 family receptors in the mesolimbic pathway
288
What are the side effects of "designed drug" antipsychotics (ex. chlorpromazine/haloperidol)?
Block receptors in the mesocortical, nigrostriatal... leading to motor impairments
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What subtypes of DA receptors are often found in the mesolimbic pathway?
D3 and D4 sub-type (members of the "inhibitory" D2 family)
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What is the function of 2nd generation antipsychotics (atypical antipsychotics, ex. clozapine)?
Target D3 and especially D4 subtypes of D2 family
291
What are the side effects of 2nd generation antipsychotics (atypical antipsychotics, ex. clozapine)?
Motor impairments, weight gain, negative immune function, increased cholesterol, lower seizure threshold
292
What is the newest antipsychotic and what is its function?
Lumateperone - 5HT2A agonist with weak D2 receptor binding
Agonist presynaptically and antagonist postsynaptically
293
How does Lumateperone treat schizophrenia and depression associated with bipolar disorder without reducing DA release?
Inhibits normal DA feedback inhibition of DA release
294
What are the side effects of Lumateperone?
Some dyskinesia, little nausea and dizziness
