Lecture 3 Flashcards

Question

What are interneuron APs?

Answer 1

``` • Not well understood • Conduction is Passive and decremental • Function to integrate neural activity in brain structure – Visual cortex • No axons • No AP • Small ```

Answer 2

• Hodkin-Huxley model based of squid neurons – Not all cerebral neurons behave the same way • More complex than model motor neurons • Some cerebral neurons: – Fire AP continually without input – Axons actively conduct graded signals and AP – AP duration, frequency and amplitude different across neuron types – Do not display AP – Dendrites can conduct AP • Comparison with motor neurons with caution

Answer 3

``` • Axodendritic – Axon ->dendrite – Most common • Axosomatic – Axon->soma • Axoaxonic – Axon -> axon – Mediate presynaptic inhibition or facilitation • Selectively influence synapse rather than entire neuron • Dendrodendrtic – Dendrite -> dendrite – Reciprocal • Can be transmitted in either direction • Dendroaxonic – Dendrite -> axon • Directed synapse – Site of NT release close to post synaptic contact – Most common • Undirected synapse – Site of release and contact far – Varicosities • String of beads – Common for monoamines (NE, DA) – Neuroendocrine system releases neurohormones into blood stream ```

Answer 4

Shaft | Spine

Answer 5

``` 1. 2. 3. 4. 5. • Neurotransmitter molecules • Early studies on NMJ – Muscles large – Muscles only receive one synapse – Acetylcholine (Ach) 1. AP reaches end of axon terminal 2. Calcium enters cell 3. Release NT into cleft (exocytosis) 4. NT binds receptors 5. Receptors influence post synaptic neurons • Ion permeability (ionotropic) – Create EPSP or IPSP • Intracellular signalling (metabotropic) – Longer lasting 6. NT degradation/recycling ```

Answer 6

* Enzymatic conversion of amino acid precursors | * Presence of enzyme dictates which type of NT are released from cell

Answer 7

Peptides | Processed by enzymes

Answer 8

• Small molecule – Classical neurotransmiPers – Punctateeffects – ReleaseinpulseforeachAP – Synthesized in cytoplasm and golgi apparatus of terminals • monoamines: Vesicles stuffed with precursor amino acid and synthesizing enzymes enroute to terminal – Released into cleft • Large molecule – Neuropeptides – Released gradually in response to increases in AP – Widespread effects – Released into ECF, ventricles or bloodstream – Neuromodulators – Synthesized in cell body, packaged in vesicles and then transported to terminal

Answer 9

``` • Secretory vesicles – Proteins synthesized in RER – Transported to golgi – Bud off golgi to form vesicle – Fast antergrade axonal transport – Transporter proteins actively pump NTs into vesicles • Example: VAchT • Small clear core vesicles – Contain small molelcule NT – 40-60nm DIAMETER • Large dense core vesicles – Contain neuropeptides – 90-250nmdiameter • Coexistence – More than one type of NT synthesized and released in neuron • Normally mix of small and large NT ```

Answer 10

``` • Anterograde to axon terminal – Motor proteins • Kinesin – Uses series of attachment detachment steps – Microtubule highway system • Colchicine and vinblastine disrupt MT and prevent transport – Requires energy – Requires calcium – Speed of transport is 0.5-1.5 cm/hr ```

Answer 11

1. AP in axon terminal 2. Open voltage gated Ca++ channels – Clustered in active zone 3. Increase calcium influx 4. Activates proteins responsible for – Mobilizing vesicles • Synapsin removes vesicles from mt network – Fusing vesicles with synaptic membrane • Synaptotagmin • Snap25 • Syntaxin 5. Vesicles move to active zone 6. Vesicles dock onto synaptic membrane 7. Fuse with synaptic membrane and release NTs into cles – Exocytosis

Answer 12

``` • Local resynthesis of synaptic vesicles • Pit formation – Kiss and run hypothesis • Direct recycling • Clatharin coating – Endocytosis – Cycle through endosomal compartment – Indirect recycling ```

Answer 13

• Pre and post synaptic cell • Specific for neurotransmitter – Multiple receptor subtypes for each NT • NT act differently in different areas of brain • Distribution varies across CNS – NT can only influence cells with receptors – Ligand = molecule specific to receptor • Example: Ach is a ligand for Ach receptor

Answer 14

``` • Ligand–gated ion channels – NT can open or close ion channel • Influx or blockade of of sodium, chloride, potassium, or calcium • Fast acting • Generate EPSP or IPSP • Found post ```

Answer 15

``` • 7 TMD • G protein coupled – Second messenger signalling • Change gene expression • Modify existing proteins • Open or close ion channels – Indirectly induce IPSP or EPSP • Slow acting • Long lasting changes • More varied and diffuse effects • More prevalent than ionotropic • All neuropeptide receptors are metabotropic • Found pre and post synaptically – Presynaptic inhibition/ facilitation ```

Answer 16

``` • EPSP OR IPSP (ionotropic) – Summated to initiate or inhibit AP generation in post synaptic cell • Activate second messenger systems (metabotropic) – 1st messenger=NT – 2ND Messenger= Calcium, DAG, IP3, cyclic AMP (cAMP) • Initiate intracellular cascades • Open other ion channels • Long lasting changes in: – Synapse structure – Gene expression » Think effects of epigenetics – Cell survival ```

Answer 17

``` • Metabotropic • Bind to own neuron’s NT • Presynaptic • Provide feedback – Reduce release when NT high – Increase release when NT low ```

Answer 18

``` • Transporters on cell neurons and/or glia pick up NT from synaptic cles – In the cell: • NTs are repackaged into vesicles for future release • NTs are degraded by enzymes intracellularly – Excreted » Monoamines – Used as precursors for NT synthesis » Glutamate/GABA – Used as precursors for energy production » Glutamate ```

Answer 19

• Some NTs do not have transporters for reuptake – Enzymes degraded in cleft • Acetylcholine – Acetylcholinesterase » Inhibitors: pesticides, nerve gases venoms, reversible inhibitors used for treating ad • Some NTs are taken back up into cell but degraded in cytosol – Dopamine • Mao

Answer 20

* NT reuptake can provide more NT to be repackaged and released immediately * Some NT s can be broken down to form more of the same NT or used as a precursor to form different NT

Answer 21

``` Astrocytes – Domains • Even distribution • Little overlap of astrocytes • Coordinate activity of synapses in domain • 40K processes=high potential to regulate – Modulate neuronal activity • Have NT receptors • Release NT – Tripartite synapse • Presynaptic, post synaptic and astrocyte cell – Uptake glutamate • Reduce excitotoxicity • Stimulate energy provision to neuron – Support ongoing neuronal activity ```

Answer 22

``` • Made up of connexin – Mutations and disease • Connect cytoplasm of 2 adjacent cells – Second messengers – Electrical signals • Electrical synapse – Faster than chemical synapse • also found in interneurons • Function to synchronize activities of similar cells – interneurons ```

Answer 23

• Small molecule • Fast acting directed synapses • Byproducts of intermediary metabolism

Answer 24

``` • Carry 2 negative charges • Dendrite major receiving area – Require a lot of input for excitation • Glutamate – Most prevalent in CNS – Ionotropic • Sodium, potassium, and calcium – Metabotropic • Gs and Gq • Aspartate • Generate EPSP ```

Answer 25

``` • Inhibitory – Carry one negative charge – Soma major receiving area • Require less input for inhibition – GABA • Synthesized from glutamate • Most prevalent inhibitory NT in CNS • Interneurons • Ionotropic – Chloride influx or potassium efflux • Metabotropic – Gi/o – Glycine • Mainly in spinal cord • Ionotropic receptor – Chloride ions – Generate IPSP • Can generate EPSP in certain conditions ```

Answer 26

``` • Excitation vs inhibition • Yin and yang • Epilepsy – Too much glutamate – Not enough GABA • Learning and memory – Wire together fire together – Too much GABA or not enough glutamate impairs memory ```

Answer 27

``` • AKA biogenic amines • MAO degrades • Catecholamines – Dopamine(DA) – Norepinephrine(NE) – Epinephrine (adrenalin) (EPI) – Precursortyrosine • Indolamines – Serotonin (5-HT) – Melatonin – Precursortryptophan • Histamines • Diffused effects – Metabotropic receptors – Released by varocosities • Psychotropic drugs mimic or affect these systems ```

Answer 28

``` • Modulators in PNS and CNS • Several receptor subtypes • EPI only released in PNS – Sympathetic nervous system • Fight or flight • Increase energy availability • NE and DA found in both PNS and CNS – Cant cross BBB – Stay and made in CNS/PNS ```

Answer 29

``` • NE - Locus coereleus -Stress/anxiety -Vigilance -NE enzymes only in NE neurons • DA restricted distribution - Nigrostriatal system • Movement and reward - Dorsal mesostriatal pathway • Movement intiation – Parkinson’s disease - Ventral nigrostriatal pathway • Positive incentive/reward Mesolimbic cortical • Projects to limbic structures • Role in schizophrenia - Periventricular • Originate in hypothalamus – Motivated behaviours hunger, thirst and sex -Tuberalhypophyseal • Lactation -DA neurons do not have enzymes to further convert to NE or EPI ```

Answer 30

``` • Serotonin (5HT) – Modulatory – Several receptor subtypes – Distributed in 2 clusters • Raphe nuclei – Provide 80% of 5HT to forebrain • Caudal system – Sensory and motor function in spinal cord – Appetite, sleep and aggression • Decreased 5-HT increases aggression • High 5ht decreases carbohydrate appetite • Decreased 5-ht = insomnia – LSD ```

Answer 31

``` – Fluctuates with light cycle • Signals seasonal day length – Regulate circadian rhythms – Secreted in darkness • TV, laptop, cellphones at night? – Cause drowsiness/sleep • Used as sleep aid ```

Answer 32

``` • First identified in NMJ – Botox – curare • Modulatory – Several receptor subtypes • Different CNS and PNS distributions • Nicotinic – Motor – Curare • Muscarinic – In ANS – atropine • Simple synthesis and degradation – Unique synaptic degradation (AchE) – Easy synthesis acetate+choline (ChAT) • Role in learning and memory – Alzheimer’s disease – Dietary choline – Atropine (mAchR antagonist) ```

Answer 33

``` • Soluble gases – Nitric oxide (NO) – Carbon monoxide (CO) – Both synthesized in neural cytoplasm – Retrograde transmission – Rapid diffusion to ECF • Cross membranes • Stimulate second messenger production – Difficult to study • Rapid breakdown • Exist for seconds ```

Answer 34

``` - Receptors highly distributed – Anadimide • Sanskrit for “eternal bliss” – Pain reduction – Increase appetite – FaPy acids cross membranes – Retrograde transmission ```

Answer 35

Actions depend on amino acids, sequence | Loosely grouped: pituitary, hypothalamus, brain-gut, opiod, misc

Answer 36

Agnostic - mimic efforts of the neurotransmitter Antagonists - blocks the effect of the neurotransmitter Alter NT activity at any point in cycle

Answer 37

• Influential lines of research • Treatments for neurological or neuropathological disorders – Anxiety – Depression – Schizophrenia – Parkinson’s and Alzheimer’s disease – Epilepsy • Drugs target specific receptors for specific effects • Drug discovery and endogenous agonist discovery give insight into brain mechanisms of pleasure and pain – Opioids

Answer 38

* Legal status irrelevant * Ease of crossing BBB * Habitual use of a drug despite consequences and efforts to stop * Physical vs psychological dependence * Rewarding brain stimulation and CPP * Mesotelencephalic dopamine system

Answer 39

``` • Endogenous – Endorphin and enkephalin • Exogenous – From opium poppy resin (morphine/ heroin) • Produce analgesia • Act in PAG, hypothalamus, limbic ```