ANAT242 - module 3 quizlet

How are memories stored

By strengthening conections of neurons and increasing gene expression of the neurons up regulating receptors

K+ concentration in cell

1:20 more inside

Na+ conc in cell

10:1 more outside

Ca2+ conc in cel

Ca2+ 10000:1 more outside so little Change in conc makes. Big difference

Cl- conc in cell

11.5 : 1 more outside

sodium potassium pump

membrane protein that pumps K+ into the neuron and Na+ outside if level get two hight the other way the put will break down ATP to make energy to pump against gradient

calcium pump

actively transport ca2= against gradient out of cell can also have intracellular calcium uptake of release from ER or mitochondria

Hyperpolrization

inhibits the neuron and from Cl- entering

Depolarization

excites neuron and Na+ goes into cell

Action potentials variations they can have

distribution of ap intensity and duration

ap signal transduction

do not diminish self propagation and size and duration is fixed over time

5 steps in AP

meet threshold na+ flows in voltage gated Na+ channels close K+ channels open chemically gated then it closes and pumps restore to equilibrium

spatial and temporal summation

we already know

difference between electrical and chemical synapses on a tem image

electrical less darkening as no joining proteins but have mitochondria

how electrical synapses work

current flows from one neuron to next via gap junctions allow ions to pass equally in both directions very fast allows for syncronization

structure of a gap junction

made of 6 connexions that make up one gap junction with pore in middle

pre synaptic events at synapse

voltage gated ca2+ channels open then Ca2+ influx cause neurotransmitter exocytosis in to synapse

small synaptic vesicles what they contain

50nm diameter clear (so no large proteins) membrane bound contain classical neurotransmitter (glutamate, GABA, glycine)

Large dense core vesicles

100nm dark (so large proteins in it) membrane bound contains (catecholamine, neuropeptides, neurotrophins) LIKE ADRENALINE

pools of small synaptic vesicles and with recycling

have readily releasable pool at the membrane ready to be exocytosed

reserve pool with is away from active zone and attached to cytoskeleton (actin filaments)

recycling pool (diffusion of neurotransmitter back into presynaptic membrane) back to reserve pool after

where are small synaptic vesicles formed

formed in the Golgi apparatus then along microtubules (axon) to reserve pool

how are small synaptic vesicles formed

filled in nerve terminal e.g glutamate filled vial VGLUT transporter with transports glutamate and H+ ions into cells with gradient generated by the H+ pumps pumping H+ out of cell

do LDCV play a big role in the CNS (Large dense core vesicle )

no more modulation and local diffisuion they are slow and act on G protein coupled receptors

synthesis pathway of Large dense core vesicles

1.) synthesis and modification of neuropeptides in rough endoplasmic reticulum or Golgi apparatus 2.) packaging (pro-peptide and Golgi apparatus 3.) axonal transport 4.) cleavage of pro-peptide 5.) release

(slow recycling) as has to go back and forth

LDCV neurotransmitter release

dosent need to be docked mobile can occur via membrane fusion dosent have to be at active zone

two primary locatiocations and example of LDCV

neurosecretory cells and neuroendocrine cells

e.g secret cromifin cells in to the blood stream to release ADRENALLIN

Chromafin cells

neuroendocrine cells in medulla of adrenal gland have lots of LDCV with cromofinn granules in them release shii in to blood stream

external proteins on a vesicles

VGLUT, Rab, synapsin, synaptobrevin, syntaxin

Rab proteins in exocytosis

translocation and docking requires Rab proteins (small GTP binding proteins) to bind first so it can then bind to t-snare on membrane

Exocytosis with V-snare and T-snare with SNAP25

synaptobrevin (v-snare) on vesicle membrane and syntaxin (t-snare) on the plasma membrane both wrap around snap25 with pulls the two synaptic vewssicles together

synaptotagmin with exocytosis

synaptotagmin senses calcium and triggers the vesicle fusion and release couples ca2+ influx and vesicle fusion so it is need it pulls them together the membranes

Ca2+ binds to synaptoagmin

Clathrin-mediated endocytosis

clathrin assists in the formation of a coated pit on the inner surface of the plasma membrane of the cell with buds into the cell to form a coated vesicle

Clathrin assembly in endocytosis

they made of 3 large and 3 small polypeptide chains Thant go together to make a basket AP2 adaptors link clathrin to the cell membrane

dynamin in endocytosis

is a GTPase forms a collar then GTP hydrolyses then gets longer and tighter pinching the vesicle off

how does botulin toxin A work on SNAP25 and the other heavy chain

heavy chain irreversibly presynaptic cholinergic receptors

light chain binding to SNAP25 preventing exocytosis/ fusion with the membrane

synaptobrevin and syntaxin affected by botulinum toxins

atacks both mainly synaptobrevin as it is a v-snare and stops its cleavage so stops fusion with membrane

tetanus toxin affecting vesicle release

presynaptic membrane on NMJ binds inhibitory neurons cleaves synaptobrevin (vsnare) stopping vessicle release in inhibitory neurons

a-latrotoxin effect on small synaptic vesicle release

its from black widow spiders

and binds to neurexin and forms a pore in cell membrane letting Ca2+ in causing SSV release causing muscle spasms

a-latrotoxin effect on Large dense core vesicle release

they controlled in different way so Ca2+ influx dosent do anything

Synapsin with Ca2+ on small synaptic vesicle release

only on SSV not LDCV controls vesicle mobility

synapsin binding vessicles in reserve pool and how it is released

synapsin on SSV binds to actin in cytoskeleton synapsin phosphorylated by activating protein kinase (CaMKII) when cell depolarises and the reserve pool is released

what if synapsin isisnt present on SSV in excititory synapses

no reserve pool of vesicles so less glutamate release

what if synapsin isisnt present on SSV in inhibitory synapse

loss of reserve pool so no GABA

what happens if you delete single of multiple SYN gene removed for synapsin

can get schizophrenia like phenotype as no inhibitory so it can cause epilepsy or autism

4 classes of neurotransmitters and examples

Type 1 amino acids (glutamate, GABA, glycine(SSV)) type 2 amines and purines (aCh, catecholamines, histamines, serotonin(SSV)) type 3 neuro peptides (neuropeptides) type 4 gases (NO, CO)

criteria for neurotransmitters

In brain in synaptic vessicles enzymes for it in presynaptic terminial receptors for it respond to depolrization can be mimicked or inhibited uptake mechanism

what is dopamine involved with in the body

movement, mood , attention, addiction, mood, cognition, reward. and low of it causes Parkinson's disease

dopamine pathway that controls movement

substrata nigra to striatum nigrostriatal

substantial nigra in Parkinsons disease

los of dopamine neurons

immunohistochemistiry with dopamine

dopamine then have antigen A added then secondary antibody (markers) are added with are visible

Diaminobenzadine (DAB) stain

dopamine the antibody bind to that biotin secondary antibody bind to that then avidin and then peroxidase added

peroxidase enzyme added turns DAB brown when it is added if these things are bound to dopamine

dopamine synthesis

tyrosine hydroxylase to l-dopa to dopamine

so if find any of these you have dopamine

how to test if cells respond releasing dopamine when electrically stimulated

put cell in thing and stimulate and test if dopamine is released

agonists and antagonist of dopamine

agonists bromocriptine (treat parkinsions)

antagonists haloperidol (treat schizophrenia)

L-DOPA treatment of parkinsions

L-dopa cross BBB but dopamine dosent with cardopa so it dosent go to dopimine in body then crosses BBB but cardopa dosent

what enzyme degrades dopamine

monoamine oxidase in pre synaptic terminal

cocaine and amphetamines effect on dopamine

stop reuptake so prolonged dopamine action

what type of receptors are slow acting and how many transmembrane domains

metabolic receptors made from 7-transmembrane domains G protein coupled receptors can either regulate ion channels by second messenger systems phosrolation may be inhibitory or excitatory

Excitatory dopamine receptors

D1 and D5 Gs stimulated by adenylate cyclase

Inhibitory dopamine receptors

D2 and D4 inhibition of adynalyate cyclase Gi inhibitoy

location of dopamine receptors in the brain

substantia nigra to striatum ventral tegmental area to nuclues accumbance and limbic system

the ventral segmental area with dopamine

VTA projects to uncles accumbens reward area e.g opium cocaine and anphetamine block reuptake with increase DA at synapse

VTA in drug addiction

down regulation with prolonged use VTA also implicated in psychotic behaviour

how can a neurotransmitter transmitter have multiple differ actions

multiple differ receptor subtypes and locations

Gs dopamine receptors

D1 and D5 stimulate AC activate PKA

Gi dopimine receptors

D2 and D4 inhibit AC activate PKA

Enzyme linked receptors two types

enzyme part of the receptors it has 2 transmembrane domains and they dimerise once molecule binds catalysing enzyme

molecule binds to one transmembrane domain wich them activates stuff to then do enzyme

BDNF and exercise

brain derived neurotrophic factor is required for brain development high levels in hippocampus role in plasticity exersize inhanses BDNF

what receptor do do neurotrophins bind to

TrkB receptors wich are enzyme linked receptors

BDNF production and release

large peptide (proBDNF) made in ER packaged into LDCV in Golgi

release dependant on Ca2+ influx

proBDNF promotes cell death and is released however turns into mature BDNF wich helps cell growth

has effect on local ion channels or GPCR which activate protein synthesis of change gene expression

endocannabinoid receptors

CB1 and CB2 small soluble lipids bind endogenous ligand binds and is synthesised on demand by Ca2+ influx

it affects presynaptic receptors and do multiple things

GABA A

inotropic

GABA B

Metabotropic

what is GABA and how is it made

inhibitory amino acid GADs enzyme synthesis GABA so can use them as markers for presence of GABA

structure of GABA A receptors

5 subunits to form Cl- ion channle with allosteric binding site for GABA wich opens it

GABA A receptors what does Cl- influx do

IPSP reducing anxiety

GABA B receptors

are a G-protein coupled receptor to put K+ channels in membrane so K+ goes out repolerizing

what enzyme breaks down AcH in synapse

Acetylcholinesterase (AChE) and CHAt synthesises it

muscarinic AchR structure

4 transmembrane domain GPCR muscrin heart muscle and slaviary glands glia

metabolic changes

Nicotinic AchR

ion channles sensitive to nicotine ligand gated fast at NMJ Na+ and K= change

in vitro

cellular and molecular models e.g Hippocampal slices cells in culture

In vivo

behaviour in simple vertebrates

advantages for using invertebrates in modelling stuff

rapid life cycle/ small genome small nervous system easy to identify circuits large neurons

e.g Aplysia California can see its organelles

Aplysia California model with learning and memory

stimulus to siphon causes gill to withdraw this reflex undergoes habitation but if shocked once it lasts longer the touches and bigger reflex

presynaptic facilitation

gains increased sensitivity as first enhances neurotransmitter release and then it alters gene expression

how the single tail shock works with presynaptic facilitation with increasing neurotransmitter

L29 releases serotonin activates 5HT presynaptic receptor formation of cAMP activate PKA release neurotransmitter

how the single tail shock works with presynaptic facilitation with changing gene expression K+ channels

PKA increase phosphorylation of K+ channels and they close so prolonged activation

long-term potentiation

an increase in a synapse's firing potential after brief, rapid stimulation. Believed to be a neural basis for learning and memory.

what happens when Hippocampal lesion

rodents show impaired performance and can't learn no LTP

how synapses move through hippocampus (trisynaptic circuit)

entorhinal cortex dentate gyrus CA3 (mossy fiber synapse) CA1 (Schaffer collateral synapse)

AMPA receptors and there structure

ligand gated (glutamate) fast depolrization Na+ channle (so happens first to get Mg2+ out) 4 subunits

NMDA receptor

ligand gate glutamate and glycine slightly slower than NMDA as has to get Mg2+ out Ca2+ and Na+ channle Ca2+ sets off intracellular signalling like more AMPA receptors made

AMPA receptors structure

extracellular N terminal and the ligand glutamate binds in the clam shape thing 4 transmembrane domains

GluA2/3

if receptor has will be Na+ channle if not will be Ca2+ channle

how is mobilisation of synaptic vesicles increased

PKC

how is the gill reflex strengthend

Ca2+ channels opening so greater Ca2+ influx

LTD

from lots of small frequent stimulation

reward dopamine system

VtA to nucleus accumbance

common site of drug targets opioids stimulate it and cocaine and amphetamines block reuptake

how presynaptic endocanabinod receptors work

ca2+ influx on post synaptic side then causes endocanabinoid release that activate presynaptic CB1 receptors

how GABA is synthiszed

GABA nergic neurons have glutamate acid decarboxylase (GAD) wich synthesis GABA