Synaptic Transmission and Neural Plasticity Flashcards

Question

Acetylcholine formation, degradation, and reuptake

Answer 1

* Choline acetyltransferase (ChAT, CAT) converts choline+ Acetyl CoA (coenzyme A) into acetylcholine. * packaged into vesicles by vesicular acetylcholine transporter (VAChT). * rapidly degraded in the synaptic cleft by acetylcholinesterase (AChE) * Choline is transported back into the presynaptic terminal and converted to acetylcholine

Answer 2

* AChE (Acetylcholinesterase) inhibitors * blocks the breakdown of ACh, prolonging its actions in the synaptic cleft * **Neostigmine:** _treatment of myasthenia gravis (MG)_ * __prolongs the present of ACh which helps the symptoms of the disease

Answer 3

* Follow the secretory pathway and NOT released in the same manner as small molecule transmitters * dense-core vesicle fusion and exocytosis occurs as a result of _global elevations of Ca2+_ (sustained or repeated depolarization or release of Ca2+ from intracellular stores) * neuropeptide vesicle membrane recycled but not refilled * bind to and activate the receptor on the postsynaptic neurone * neuropeptides signalling is terminated by diffusion from site of release and degradation by proteases in the extracellular environment * release is slower than small-molecule release and signals may be maintained for longer

Answer 4

1) Nitric oxide made in postsynaptic neuron by Nitric oxide synthase (activated by the binding of Ca2+ and calmodulin) 2) The gas is not stored but rapidly diffuses from its site of synthesis. Diffuses between cells (into presynaptic cell - retrograde transmitter) 3) Activates guanylyl cyclase which makes the second messenger cGMP 4) Within a few seconds of being produced NO is converted to biologically inactive compound (switching off the signal) 5) Potentially useful for coordinating activities of multiple cells in a small region (tens of micrometers)

Answer 5

- small lipids which cause reduced GABA release at certain inhibitory terminals - e.g *Cannabis sativa* (the active component of marijuana)

Answer 6

a type of neurotransmitter receptor that contains a neurotransmitter binding site and an ion channel * it is a type of ligand-gated channel * in the absence of a neurotransmitter, the ion channel component of the protein is inactive * can be an EPSP or an IPSP reaction that the channel stimulates * most inhibitory neurotransmitters bind to Cl- ionotropic channels

Answer 7

a neurotransmitter receptor that contains only a neurotransmitter binding site: no ion channel component * can be coupled with G-protein either directly or via a second messenger * binding triggers uncoupling of heteromeric G-protein on the intracellular surface * this transduces a signal across the cell membrane

Answer 8

- what ions are fluxed

Answer 9

- the rate of flux helps determine the magnitude of the effect

Answer 10

they flux Na+ causing an EPSP, these are the three receptors that respond to glutamate * **NMDA:** * ****agonist: N-methyl D-aspartate * antagonist: APV (2-amino-5-phosphonovaleric acid) * **AMPA** * ****agonist: AMPA * antagonist: CNQX * **Kainate** * ****agonist: Kainic acid * antagonist: CNQX

Answer 11

- NMDA receptors are responsible for late-phase EPSP - only activated in an already depolarized membrane in the presences of glutamate and glycine 1. Slow opening channel – permeable to Ca2+ as well as Na+ and K+ 2. requires an extracellular glycine as a cofactor to open the channel 3. it is also gated by a membrane voltage * Non-NMDA receptors (AMPA, and Kainate) have to be activated in advance to produce the appropriate voltage for the NMDA receptor to be activated * Mg2+ ion plugs pore when the membrane is at its resting potential * When the membrane depolarizes Mg2+ is ejected from the channel by electrostatic repulsion which allows conductance of the other cations

Answer 12

* Channel Blockers * these drugs produce symptoms that resemble hallucinations associated with Schizophrenia * Dizocilipine (MK801) * Phencyclidine, ketamine * Remacemide * Memantine * Mg2+ * Drugs that enhance current flow through NMDA channels * Glutamate excitotoxicity * excessive Ca+ into the cell activated Ca-dependent enzymes that degrade proteins lipids and nucleic acids * this type of cell damage occurs after cardiac arrest, stroke, oxygen deficiency and repeated intense seizures (*status epilepticus)*

Answer 13

* Glutamate - excitatory * GABA(A) - inhibitory (brain) * Glycine - inhibitory (spinal cord and brain stem) * Nicotine - excitatory at NMJ (neuromuscular junction), excitatory or modulatory in the CNS (nicotinic receptors) * Serotonin -excitatory or modulatory * ATP- excitatory

Answer 14

* Norpinpherine: Increase protein phosphorylation * Glutamate: Increase protein phosphorylation and activate calcium-binding proteins * Dopamine: Decrease protein phosphorylation

Answer 15

1) in resting-state the heteromer is bound to GDP 2) on binding of a ligand to the receptor the GDP is switched for a GTP and the heteromer splits in two 3) the Ga subunit and Gbg complex divide and diffuse separately through the membrane 4) these individual entities are able to stimulate the activity of other effector proteins 5) alpha subunits have intrinsic GTP-GDP enzymatic activity allowing the signal to be transient: the break down from GTP to GDP switches off its activity 6) at this point the heteromer recomplexes and awaits activation by ligand binding to another receptor.

Answer 16

* 20 alpha subunits * G_s: stimulates adenylyl cyclase: increases the activity of cAMP and Protein Kinase A * Stimulatory Beta receptor * G_i: inhibits adenylyl cyclase: inhibits cAMP and Protein kinase A * Inhibitory alpha-2 receptor * G_q: stimulates phospholipase C (other fc) * Beta gamma complexes (5 beta, 12 gamma) * activate K+ channels directly * the mode of action for muscarinic ACh receptors in heart and the GABA receptor

Answer 17

* G_q activates phospholipase C (PLC) * converts PIP₂ into IP₃ and diacylglycerol (DAG) * DAG activates protein kinase C (PKC) and IP₃ releases Ca²⁺ from internal stores * which activates Ca²⁺ dependent enzymes

Answer 18

* **autoreceptors** regulate release of transmitter by modulating its synthesis, storage, release or reuptake * e.g. phosphorylation of tyrosine hydroxylase * **heteroreceptors** (axoaxonic synapses or extrasynaptic) regulate synthesis and/or release of transmitters of other ligands receptors (not directly the neurotransmitter) * e.g. NE can influence the release of ACh by modulating α-adrenergic receptors

Answer 19

they change the firing pattern or activity * increase or decrease the rate of cell firing (directly by action at ligand-gated ion channels or indirectly G -protein or phosphorylation-coupled channels) * long term synaptic changes

Answer 20

* metabotropic glutamate receptors * GABA_(B) receptor * muscarinic acetylcholine receptors * dopamine receptors * noradrenergic and adrenergic receptors * serotonin receptors * neuropeptide receptors

Answer 21

an enzyme-linked receptor found in neurons * Transmembrane proteins with intrinsic tyrosine kinase activity activated by _neurotrophin_ binding (e.g. NGF, BDNF) * on activation it autophosphorylates * it phosphorylates regulatory subunits * this starts the signal transduction cascade

Answer 22

* G-protein coupled receptor (metabotropic) * Heart tissue: mAChR -\> G-protein -\> K+ channels -\> hyperpolarisation (m=muscularinic slower) * Ligand-gated channel (ionotropic) * Skeletal muscle: nAChR -\> Na+ ion channels -\> depolarisation (n= nicotinic faster)

Answer 23

they flux Cl-, which causes IPSP, hyperpolarizing the postsynaptic neuron * prevents postsynaptic neuron from firing unless there is sufficient glutamate stimulation to overcome the hyperpolarization (the refractory period)

Answer 24

* Group I: mGluR1+5 Gq * somatodendritic: largely excitatory * Group II: mGluR2+3 Gi * somatodendritic & nerve terminals: reduce neuronal excitability * Group III: mGluR4,6,7+8 Gi * Nerve terminals: reduce neuronal excitability

Answer 25

* Objects are internally represented by cortical cells that are reciprocally interconnected in a **cell assembly** * When an external stimulus is encountered the cell assembly is activated, and persistent activation strengthens the connections of the cell assembly * so much so that after learning even if the stimuli is only partially present, a few activated connections can cause the whole assembly to be activated and the initial stimuli is recalled i.e circle

Answer 26

If the activity of strong synapses is sufficient to trigger an action potential in the neuron, the dendritic spike will depolarize the membrane of dendritic spines, priming NMDA receptors so that any weak synapses active at that time will become strengthened.

Answer 27

* Neurons that fire together wire together * Neurons that fire out of sync lose their link - strengthening and weakening synaptic connections in the brain provides a means for learning and memories can be formed

Answer 28

* **Temporal**: Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS) * **Associative:** simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation) * Coincidence detection: “Cells that fire together wire together” * **Specific**: LTP at one synapse is not propagated to adjacent synapses (input specific).

Answer 29

* Ca2+ entry through the NMDA receptor leads to activation of: * Protein kinase C * Calcium calmodulin-dependent protein kinase II (CaMKII) * Phosphorylates existing AMPA receptors, increasing their effectiveness * Stimulates the insertion of new AMPA receptors into the membrane

Answer 30

* Ca2+ entry through the NMDA receptor leads to activation of * Calcium calmodulin-dependent protein kinase II (CaMKII) * CaMKII has an autocatalytic activity - becomes phosphorylated * When phosphorylated is constitutively active - no longer requires Ca2+ * Maintains phosphorylation, insertion of AMPA receptors etc. after the depolarizing stimulus has receded * This is a _molecular switch_ which maintains increased excitability of neuron for minutes to hours

Answer 31

* Postsynaptic neuron can feedback to presynaptic neuron by retrograde neurotransmitter - Nitric Oxide (NO) * Ca2+ through the NMDA channel activates Nitric oxide synthase * NO diffuses from the site of production and activates guanylyl cyclase in the presynaptic terminal * Guanylyl cyclase produces the second messenger cGMP * Signal transduction cascade leads to increased glutamate release from the synaptic button

Answer 32

- Late phase LTP is long-lasting LTP that can last hours, days or months - This requires new protein synthesis and can involve morphological changes and the establishments of new synapses * Ca2+ activated signal transduction cascades activate new protein synthesis from dendritically localized mRNAs * this filter back to the cell body to stimulate new gene transcription (CREB -mediated), protein synthesis and recruitment of new proteins to the synapse

Answer 33

* is caused by Low frequency stimulation (LFS: 100x 1 Hz): there is a decrease in EPSP amplitude on further stimulation at a low frequency * Same players involved: * NMDA dependant process * AMPA receptors are de-phosphorylated and removed from the membrane * Prolonged low-level rises in Ca2+ activate phosphatases rather than kinases

Answer 34

* NMDA receptor activity in the hippocampus essential for both LTP and spatial learning * AP5 - NMDA receptor antagonist * blocks hippocampal LTP * blocks learning in the Morris Water Maze

Answer 35

* Alcohol is an NMDA receptor antagonist (as well as other sites) * Blackouts and amnesia caused by drinking * directly blocking normal LTP processes * Alcohol disrupts hippocampal theta rhythms and disrupts short term memory. * Chronic alcoholism and associated nutritional deficiency can result to Korsakoff syndrome or psychosis: loss of recent memory, and tendency to fabricate accounts of recent events (confabulation).

Answer 36

* Indirect agonist of GABA_A receptors: * binding increases the receptor affinity for GABA * increase frequency of channel opening * anxiolytic and hypnotic drugs * Side effect to anxiolytic and sedative properties: * anterograde amnesia

Answer 37

* Acetylcholine projections: * Basal forebrain bundle: * Medial septum to hippocampus * Basal nucleus to cortex * Septum to hippocampus projection regulates theta waves * Scopolamine (muscarinic receptor antagonist) * suppresses theta waves and impairs spatial learning

Answer 38

* they boost cholinergic function * improve memory impairment * e.g physostigmine

Answer 39

* Inducing Factors: signalling molecules provided by other cells * freely diffusable, exerting their action over a long-range or tethered to the cell surface acting locally * They can modify gene expression, cell shape and motility. cells in different positions in the embryo are exposed to different inducing factors, can effect the final cell outcome * Competence: the ability of a cell to respond to inducing factors this depends on: * the exact set of surface receptors * transduction molecules * transcription factors expressed by the cell

Answer 40

* the process by which neurons are generated * 5th week – 5th month of gestation * Peak rate of 250,000 new neurons / minute

Answer 41

* Infinitely self –renewing * After terminal division and differentiation, they can give rise to the full range of cell classes within the relevant tissue, * e.g. inhibitory and excitatory neurons, astrocytes, oligodendrocytes.

Answer 42

* Incapable of continuing self – renewal * Capable to give rise to only one class of differentiated progeny, * e.g. an oligodendroglial progenitor cell will give rise to oligodendrocytes until its mitotic capacity is exhausted.

Answer 43

* Postmitotic, immature nerve cells that will differentiate into a neuron * formed when a precursor cell is horizontally cleaved, it contains the Notch-1 protein * the fate of the migrating neuron will be determined by * age of the precursor cell * position in the ventricular zone * the environment at the time of division

Answer 44

* Pathway selection * e.g. retinal ganglion cell reaching the correct thalamic location. * Target selection * e.g. selecting the appropriate thalamic nucleus, LGN. * Address selection * which LGN layer. The formation of the axon and dendrites is guided by the filopodia which guide the growth cone (consists of growth cones called lamellipodium) * the growth of the neuroblast is controlled by guidance cues * chemoattractant: netrin receptors towards areas with netrin * chemorepellents: robo away from slits on the midline

Answer 45

* Gradients in the expression of guidance cues and their axonal receptors can impose topographic order, * final refinement of connections often requires large scale reduction of newly formed neurons and synapses. * The protein ***netrin*** is secreted by cells in the ventral midline of the spinal cord. Axons with the netrin receptors are attracted to the region of highest netrin concentration * The protein ***slit*** is secreted by midline cells. Axons that express the **protein *robo***, the slit receptor, grow away from the region of highest slit concentration. * Up-regulation of robo by axons that cross the midline ensures that they keep growing away from the midline.

Answer 46

* Initially each muscle fibre receives inputs from several alpha motor neurons. * Over the course of development, all inputs but one are lost. * Postsynaptic AChR loss precedes the withdrawal of the axon branch. * Simply blocking a subset of receptors with α-bungarotoxin can also stimulate synapse elimination.

Answer 47

* This describes a variable time window for different skills/behaviours e.g. sensorimotor skills, language acquisition, visual perception, emotional functions to be developed. Successful completion of this period depends on * Availability of appropriate influences * Neural capacity to respond to them

Answer 48

* these are afferent terminals in the fourth cortical layer that form a series of alternating eye-specific domains * visual deprivation: there is a period of time after birth where any alterations to the stimuli available to the visual cortex will permanently affect the vision of the individual

Answer 49

In the postnatal and adult brain, significant barriers to regeneration are present. * Radial glia are exhausted and become a “lost highway” to any neuronal migration. * Cortical neurons are no longer generated and thus virtually no neurons can be found migrating into the cortex. * Neuronal plasticity becomes significantly attenuated, preventing the type of plasticity observed prior to developmental critical periods. * Interneuron progenitors and mINs disappear. * Parenchymal glia do not cross lineage boundaries and become reactive after injury and degeneration.

Answer 50

* Without neurogenesis, new events are limited by the set of sparse ‘codes’ (combinations of active neurons) provided by mature granule cells in the dentate gyrus * New neurons (shown in green) provide new sparse codes for encoding new information, while older memories are preserved because they are represented by older neurons