Lecture 4 - Neurotransmitters, Synapses, Neural Communication and Hormones

Question 1

Synapses

Answer 1

Synapses the gap between neurones where signals are passed from one to the other Electrical Synapses Chemical Synapses Pre-synaptic neurone -> post-synaptic neurone Mostly through chemical synapses Functionally and structurally different

Question 2

Electrical synapses

Answer 2

Very small gap between two neurones (2-4 nm) The facing membranes have large channels that allow ions to move directly from one cell to the other Transmission from one neuron to the next is similar to action potential conduction along the axon Very fast – no time delay Rare in human CNS (eye movements) Extremely fast Channels practically touch Very rare in humans Membranes are close together -> with a channel that allows flow from one to the other Recored from presynaptic and postsynaptic neurone -> inject current (induced action potential through adding current into the system) -> observe the volocity of transfer of information from pre-synaptic neurone to post-synaptic neurone Presynaptic cell -> as soon as current, there is an action potential trigurued (with slight delay to reach threshold) Postsynaptic cell -> current was not injected here, response seen with almost identical timing of volatage added (practically no delay) -> very fast transmition

Question 3

Aplysia

Answer 3

Neurone firing is highly syncronised Studies done on this to test this on Aplysia- release ink when trigurred/ threatening event External stimulus- tiny amount of current (painful) into tape(connected to sensory neurone) -> how long does it take to react (release ink) One neurone -> 3 neurones -> record all three to see if syncronised Testing for the current First line up = current sent through the tape Next line is the action potential Gap between stimulus and action potential but almost the same From different cells -> not connected

Question 4

Chemical synapses

Answer 4

Small gap but much larger than gap junctions (20-40 nm) Each neurone has many (typically ca 1000) synapses Slower (ca 1ms) More common and very close and syncronised not practical-> converging neurones Much larger gap (synapse)-> still very small just comparatively larger 1 to many (convergent) Neurone can impact other sidess neurones Slower-> neurotransmitter must cross then trigger action potential at threshold

Question 5

How does a chemical synapse transmit

Answer 5

1. Action potential arrives at presynaptic membrane 2. Voltage-gated Ca2+ channels open, Ca2+ diffuses into cell 3. Synaptic vesicles fuse with membrane, releasing neurotransmitter molecules into synaptic cleft 4. Transmitter binds to postsynaptic receptors, opening ion channels 5. If channel is for Na+: → depolarization = excitatory postsynaptic potential (EPSP) If channel is for Cl-: → hyperpolarization = inhibitory postsynaptic potential (IPSP) 6. EPSP/IPSP propagated along membrane

Question 6

Post-synaptic receptors

Answer 6

Receptors are membrane proteins that bind neurotransmitters Receptor specific to neurotransmitter – lock-and-key principle -> when a transmitter molecule binds to the receptor, the receptor changes shape, causing an ion channel to open Ionotropic receptors FAST These control the ion channel directly When bound to the transmitter the ion channel opens and ions flow across the membrane Also known as ligand-gated ion channels Fast because can bind imedieatley and open straight away Metabotropic receptors SLOW These also bind with the neurotransmitter but do not open the ion channel They activate G-Proteins that subsequently control the ion channel Slow because bing to a receptor which causes second messenger (protein to open gate) goes to channel - takes more time -> bind with gate and open (extra step = takes longer) Channels are specific This results in depolarization or hyperpolarization of the postsynaptic membrane Depolarization: EPSP Hyperpolarization: IPSP

Question 7

Summation

Answer 7

Strengthens action potential by combing multiple action potentials for stronger voltage Two types: Temporal= multiple stimulus in same pre-synaptic cleft summate to create larger potential Spatial= multiple pre-synaptic clefts to active on post-synaptic

Question 8

Neurotransmitter

Answer 8

A chemical released by one neuron that affects another neuron or an effector organ (e.g., muscle, gland, blood vessel)

Question 9

Properties of neurotransmitter

Answer 9

1. Synthesized (made) in the presynaptic neuron 2. Localized to vesicles in the presynaptic neuron 3. Released from the presynaptic neuron under physiological conditions -> when enough action potential 4. Rabidly removed from the synaptic cleft by uptake or degradation 5. Presence of receptor on the post-synaptic neuron 6. Binding to the receptor elicits a biological response

Question 10

Excitatory neurotransmitters

Answer 10

Acetylcholine Aspartate Dopamine Histamine Norepinephrine Epinephrine Glutamate Serotonin

Question 11

Inhibitory neurotransmitters

Answer 11

GABA Glycine

Question 12

Acetlycholine

Answer 12

Spinal cord neurons -> control muscles Brain -> regulate memory Most excitatory

Question 13

Dopamine

Answer 13

Feelings of pleasure -> brain reward system Usually inhibitory

Question 14

GABA

Answer 14

Major inhibitory neurotransmitter in brain

Question 15

Glutamate

Answer 15

Most common excitatory in brain

Question 16

Glycine

Answer 16

Mainly neurons in spinal cord Inhibitory

Question 17

Serotonin

Answer 17

Mood Appetite Regulate normal brain functions Inhibitory in pain pathways

Question 18

Neurotransmitter re-uptake

Answer 18

Continued presence of neurotransmitters in the synaptic cleft would lead to persistent EPSPs or IPSPs – even without further action potentials in the pre-synaptic neuron To avoid this, neurotransmitters are either: 1. Moved back into the presynaptic or other cells by transporters 2. Degraded/neutralised by enzymes

Question 19

Neuron communication

Answer 19

Point-to-point Restricts synaptic communication Brain areas with expanded influence over space and time Hormonal Communication - Secretes chemicals into the blood stream to affect the entire body. Interconnected neurons of the ANS - Simultaneously controls responses in many internal organs. Diffuse modulatory systems - Specific neurotransmitter

Question 20

Noradrenergic Locus Coeruleus

Answer 20

Makes some of the most diffuse connections in the brain Regulating attention, arousal, sleep wake cycles, learning and memory, anxiety, pain, mood and brain metabolism Activated by new, unexpected, non-painful sensory stimuli General arousal to interesting events in the outside world Increase brain responsiveness, speeding information processing

Question 21

Serotonergic Raphe Nuclei

Answer 21

Caudal innervate spinal cord and modulate pain-related sensation Rostral innervate brain Fire most during wakefulness Part of reticular activating system Involved in sleep wake cycles and stages of sleep Control of mood and emotional behaviors

Question 22

Cholinergic Basal Forebrain

Answer 22

General function not completely understood First cells to die in the course of Alzheimer’s disease Implicated in arousal, sleep wake cycles, learning and memory

Question 23

Dopaminergic Substantia Nigra

Answer 23

Neurons project from Substantia Nigra to striatum Control voluntary movements Degeneration results in Parkinson’s disease Ventral tegmental area projects to frontal cortex and limbic system Reward system that reinforces adaptive behaviors Motor control and Reword Dopamine nuclei in brain system Frontal lobe + prefrontal lobe -> reasoning, thinking, decisions, cognitive reasoning, reward (dopamine) Important for motor control-> parkensons get tremers etc., problems with addiction -> fault in dopamine system that is effecting motor and reward systems

Question 24

Antagonistic

Answer 24

Drugs block the effects of neurotransmitters Novacaine Caffeine

Question 25

Agonist

Answer 25

Drugs mimic or increase the effects of neurotransmitters Heroin LSD Cocaine

Question 26

Drugs effect

Answer 26

Drugs alter various stages of synaptic processing Increasing number of action potentials Release transmitters from vesicles without impulses Producing more neurotransmitter Preventing neuro transmitter release Blocking re-uptake Blocking receptors

Question 27

Abused drugs

Answer 27

Almost all abused drugs stimulate dopamine release in the nucleus accumbens Feelings of pleasure Altering neurotransmitters -> a lot do this to dopamine Effect on dopamine causes the addiction Nucleus Accumbens- Centre of pleasure and feul of dopamine-> release impulses across brain

Question 28

Meth

Answer 28

Alters Dopamine transmission in 2 ways: (1) Enters dopamine vesicles in axon terminal causing release of transmitter (2) Blocks dopamine transporters from re-uptaking dopamine This results in > dopamine in the synaptic cleft Neurones fire more often than normal resulting in euphoria Addition also caused by dopamine Difference in meth user and placebo Long term impact on brain function

Question 29

LSD

Answer 29

Serotoninergic Hallucinogen Lysergic Acid Diethylamide (LSD) Physical Effects Dilated pupils Higher or lower body temperature Sweating or chills (“goose bumps”) Sleeplessness Dry mouth Tremors Mental Effects Delusions Visual hallucinations An artificial sense of euphoria or certainty Distortion of one’s sense of time and identity Severe, terrifying thoughts and feelings Fear of losing control Panic attacks Flashbacks Severe depression or psychosis Area of brain solely to proccess vision- ocipital lobe/ visual cortex -> LSD causes brain activity all over brain (see picture) that is completely different-> Visual cortex has increased activity due to the drug (numbers are different slices of the brain across ways -> see blue lines on diagram) Large amounts of signals and proccessing causing hallucinations that seem real

Question 30

Alcohol

Answer 30

MULTIPLE EFFECTS !!! It alters neuronal membranes, ion channels, enzymes, and receptors Binds directly to receptors for: Acetylcholine Serotonin GABA Glutamate Alzimers -> impacts quality of life, larger gap in brain Alcohol for many years -> gap larger than that of alzhimers, functional and structural impacts

Question 31

Diffuse Modulatory systems

Answer 31

Regulate arousal, mood, motivation, sexual behavior, emotion, sleep, etc. Affect wide areas to make them more or less excitable or more or less synchronously active etc. Messages that must be widely broadcast through the brain use diffuse modulatory systems The brain uses many of these mechanisms each requiring a specific neurotransmitter Connections are widely dispersed throughout the brain Doesnt create signals -> amplifies it Small number of neurons - each can connect to MANY others Neurons of the diffuse system arise from this central core (in the brain stem) Neurotransmitters are released into the extracellular fluid and can diffuse to many neurons

Question 32

Hormones

Answer 32

Chemicals secreted by one cell group travel through blood to targets Released from endocrine glands

Question 33

Hormonal communication

Answer 33

9 general principles 1. Gradual, often long-lasting, effect 2. Change likelihood of behaviour 3. Hormones and behaviour interact 4. Many different hormones affect many different body parts & behaviours 5. Produced in small amounts (often in bursts) 6. Many have rhythmic release 7. Hormones interact with other hormones 8. All vertebrate hormones have similar structures, but not necessarily similar effects 9. Can only affect cells with the appropriate receptor proteins Not as fast Hormones have similar molecular sturcutre but completely different effect -> cells only effected if have specific receptor: not random Hormones can effect most of the body-> allow homeostasis (controlling internal envrioment) Controlled by hypothalumus Cannot control hormones

Question 34

How do hormones work

Answer 34

Hormones travel through the blood and influence the activity of other glands and organs They produce short- and long-term changes in various cells and organs by acting like neurotransmitters at metabotropic receptors A hormone can only influence cells that have specific target receptors for that particular hormone.

Question 35

Different hormones

Answer 35

Protein hormones Comprise amino acids Protein and amine hormones faster than steroids Bind to receptor, activate second messenger Second messenger alters cell function Steroid hormones These are derived from cholesterol from the diet Bind directly to membrane receptors Much slower Affect the long-term production of proteins within the target cells

Question 36

Hormones - negative feedback

Answer 36

Autocrine feedback Endocrine cell senses the increase of its own hormone and switches off hormone release Target cell feedback Target cell releases another substance when stimulated by the hormone which subsequently inhibits hormone release in the endocrine cell

Question 37

Endocrine system

Answer 37

All glands of the body and hormones produced by those glands by regulating the functions of organs in the body, these glands help to maintain the body’s homeostasis: cellular metabolism, reproduction, sexual development, sugar and mineral homeostasis, heart rate, digestion…

Question 38

Hypothalamus

Answer 38

Below the thalamus Forms the walls of the third ventricle It can be divided into several nuclei: each nucleus has a very specific function Integrates somatic and visceral responses in accordance with the needs of the brain Homeostasis – maintains the body’s internal environment in a narrow physiologic range Temperature, blood volume and pressure, pH, oxygen levels A tiny lesion in the hypothalamus can be lethal Three zones: Lateral, Medial, Periventricular Connections are extensive Periventricular is most highly connected to the pituitary Controls: circadian rhythms and ANS to viscera

Question 39

Posterior pituitary gland

Answer 39

Connected to the base of the hypothalamus Master gland -> produces many hormones that travel throughout the body, directing processes or stimulating other glands to produce other hormones Neuro-hormones are produced in the magnocelluar hypothalamus and released at the pituitary Oxytocin Released to initiate uterine contraction or milk let-down Can be triggered by somatic, visual or auditory stimuli or inhibited by stress Vasopressin Antidiuretic Hormone Regulate blood volume and pressure

Question 40

Anterior pituitary gland

Answer 40

Connected with hypothalamus Parvocellular neurosecretory cells release tropic factors that cause the production of hormones in the anterior pituitary Hormones: ACTH - controls the adrenal cortex (kidneys) TSH – controls the release of thyroid hormones FSH – controls growth of ovary follicles/sperm Prolactin – promotes milk production LH – promotes rupture of follicles/increase in testosterone Growth hormone – promotes growth of cells/tissues

Question 41

Oxytocin

Answer 41

Involved in reproductive and social behaviour Stimulates contractions May promote bonding (e.g. Scheele et al 2012) by influencing social distance Triggers the milk let-down reflex

Question 42

Pineal gland

Answer 42

Activated by sympathetic nervous system Releases melatonin (amine) at night Influences puberty and reproductive condition In human, important for sleep rhythms

Question 43

Synaptic vs hormonal

Answer 43