Exam 3 genes brains behavior guide

Pathway for AMPA insertion

Glutamate release, AMPA depolarization, mg2+ expulsion, nmda opens, ca2+ influx, camkii! AMPA insertion

Nmda are

Coincidence detectors

LTP phases

induction, expression, maintenance

CaMKII

Calmodulin-dependent protein kinase II; important in forming long-term memories.

Mature neurons use a combination of chemical and electrical signaling

Action potentials carry the signal along the axon, neurotransmitters carry along the synapse

The most significant advantage of chemical signaling is

Signal amplification

One neurotransmitter molecule can activate

Many second messenger molecules enormously multiplying the initial signal

Channel-Linked (Ionotropic) Receptors

Located in membrane, direct ion flow on ligand binding, AMPA, NMDA, NACHR

G protein-coupled receptors (GPCRs)

Located in membrane, second messenger cascade via G protein, mglur beta adrenergic

Enzyme linked rtk receptors

Located in cytoplasm/nucleus, bind cell permeant ligands for gene regulation, steroids receptors thyroid hormone receptors

Cell permeant signaling molecules cross

The lipid by layer and bind intercellular receptors

Enzyme linked receptors act primarily by

Phosphorylating intercellular target proteins

Dopamine

catecholamine, synthesized from tyrosine via dopa

Tyrosine pathway

Tyrosine -tyrosine hydroxilase -> L-Dopa -ddc-> Dopamine -dbh-> Norepinephrine --> Epinephrine

Glutamate

A major excitatory neurotransmitter; involved in memory, not inhibitory

GABA

a major inhibitory neurotransmitter, does not mediate ltp

Serotonin

Monoamine, not an opioid

Opioids

Endorphins / enkephalins activated

BARBITURATES affect on neurotransmitters

Affects GABA receptors

Benzodiazepines affects in neurotransmitters

Affects gaba activity

Catecholamines (epinephrine, dopamine, norepinephrine)

All derived from amino acid tyrosine via enzyme tyrosine hydroxylase

cAMP

ATP via adenylyl cyclase, activates PKA, involved in aplysia stm, CREB, phosphorylation

Ca2+

Extracellular (vgcc's & nmda) and intracellular (ER via ip3) activates camkii, pic, synaptotagmin, Calmodulin, only messenger with dual source

What's the only messenger with dual source

Ca2+

IP3

PLC cleaves pip2, triggers ca2+ release from ER, links gpcr's to intracellular ca2+ release

DAG

activates protein kinase C, plc cleves pip2, ltp coactivation with ca2+

Calmodulin

A ca2+ sensor that binds ca2+ and then binds to and activates downstream targets including camkii, it is not a ca2+ buffer

Presynaptic Ca2+ influx

Incoming action potential opens voltage-gated ca2+ channels (vgcc) triggering vesicle fusion neurotransmitter release

Protein kinases catalytic domain

Transfers a phosphate group from atp to target proteins relevant amino acid

Most protein kinases in the brain are Importnt regulators of neuronal signaling because

They can be activated by second messengers ND OTHER MECHANISMS

each kinase has a ________ that inhibits the ________

Regulatory domain, catalytic domain until activation

Tyrosine hydroxylase phosphorylation is the

Rate limiting step for catecholamine biosynthesis, phosphorylation increases enzyme activity (c)

CREB

cyclic AMP response element binding protein is phosphorylated by PKA and is critical for gene expression changes underlying short term synaptic plasticity in both physic and hippocampal ltp

Aplysia californica

Ideal mordel organism because of its large individually identifiable neurons that can be found reliably across individuals and enables precise electrophysiological recordings

How many neurons do aplysia have

20,000 neurons total

Individual Alysia neurons can be

Patch clamped and pharmacologically manipulated

The gill withdrawal reflex

Provides a well defined behavior readout of memory (B)

Serotonin is the key neurotransmitter initiating

Short term memory processes

In aplysia, serotonin is

Released by facilitatory interneurone in response to a noxious stimulus. (Tail shock)

Short term mechanism in aplysia step by step

1) Tail shock, facilitatory interneurons release serotonin onto sensory neuron terminals

2) serotonin binds to gpcr, activates adenylyl cyclase, produces camp

3) cAMP activates PKA

4) PKA phosphorylates k+ channels, channels close, prolonged presynaptic depolarization

5) more ca2+ enters presynaptic terminal, greater glutamate release, enhanced gill withdrawal reflex

synaptic facilitation; short-term memory aplysia

A temp increase in synaptic response following stimulation, does not require new protein synthesis

Short term memory

Involves synaptic facilitation only, no new proteins or structural changes

Long term memory in aplysia

Requires gene expression changes and new protein synthesis

Difference between long term vs short term memory aplysia

Long term requires gene expression changes and new protein synthesis, short term memory involves only covalent modifications of existing proteins (k+ channel phosphorylation)

Long term memory aplysia step by step method

1) repeated serotonin exposure, sustained high cAMP, PKA translocatrs to nucleus

2) PKA phosphorylated CREB transcription factor (PKA key enzyme)

3) gene expression changes, new protein synthesis

4) formation of new synaptic connections, lasting behavioral changes (days to weeks)

What occurs in long term but not short term memory

Phosphorylation of CREB

What happens in both long term and short term memory formation

Serotonin GPCR, adenylyl cyclase, PKA, k+ channel modulation

Eric Kandel

Demonstrated that learning and memory depend on long term synaptic changes and that these changes have physical, molecular and structural basis

Memory is not purely electrical

It involves molecular cascades

Both ... and ... forms exist

Short term covalent modification, long term gene expression

The synapse is the primary locus of

Memory storage

Hippocampus location

Medial temporal lobe

Hippocampus memory type

Declarative (explicit) memory, facts and episodes

Hippocampus brain system

Limbic system

Key transmitter for hippocampus for ltp

Glutamate

Process for synaptic strengthening for hippocampus

LTP

Ltp production must meet what conditions to induce

Glutamate release, AMPA activation, postsynaptic depolarization, mg2+ expulsion, ca2+ entry through nmda

Ltp pathway

High frequency stimulation, glutamate activates AMPA receptors (na+ influx, postsynaptic depolarization), depolarization expels mg2+ from nmda channel, glutamate + glycine open nmda, ca2+ binds Calmodulin, camkii enhances AMPA receptors conductance and drives insertion of new map receptors

High frequency stimulation causes

Presynaptic glutamate release

depolarization expels mg2+ from nmda channel and

Is blocked at rest, mg2+ is removed by depolarization

glutamate + glycine open nmda

Causes ca2+ influx into postsynaptic cell

Ca2+ binds to Calmodulin

Activates camkii

If mg2+ is not expelled from nmda channels

Ltp would not occur. AMPA would still mediate baseline depolarization but ca2+ cannnot enter the blocked nmda channel

NMDA is a coincidence detector

Requires glutamate binding (presynaptic) and postsynaptic depolarization to expel mg2+, only opens when both cells are active simultaneously

AMPA

Na+ primarily, fast excitatory, no mg2+ block, glutamate only agonist , depolarize membrane inserted during ltp expression, ionptropic (ligand-gated)

Nmda

Na+, k+, ca2+, slower requires coagonists, blocked by mg2+ at rest, glutamate + glycine agonists, coincidence detector (ca2+ source for ltp induction), ionotropic

Camkii has prolonged activity (1-30sec) after ca2+ stimulation due to

Autophosphorylation, it remains active even after ca2+ levels drop

PKC (protein kinase C)

Second major ca2+ activated kinase contributing to ltp alongside camkii

Late-phase LTP at Schaffer collaterals involves

(a) Ca²⁺ influx activates calmodulin; (d) sustained high PKA activity; (e) phosphorylation of CREB; (f) new protein synthesis; (g) gene expression changes..

Ltp increases

The density and volume of dendritic spines, postsynaptic sites of excitatory synapses

Donald hebb proposed that

coincident pre- and postsynaptic activity strengthens synapses — "neurons that fire together, wire together." NMDA receptors are the molecular implementation of this principle.

Hebbian plasticity

Strengthening active neurons (fire together, wire together)

Ca²⁺ has four key functions in neural signaling:

(a) presynaptic Ca²⁺ triggers vesicle fusion via synaptotagmin → neurotransmitter release; (b) activates PKA, which phosphorylates K⁺ channels or CREB (Aplysia STM); (c) activates CaMKII in early LTP → AMPA receptor insertion..

Synaptotagmins are

Presynaptic ca2+ sensing proteins that directly trigger vesicle fusion, distinct from camkii/pkc, which modulate postsynaptic receptor function

Synaptic facilitation

Temp increase in synaptic response following stimulation, cellular basis of aplysia short term memory

Donald hebbs contribution

Proposed synaptic strengthening through coincident pre and post synaptic activity, hebbian learning rule. Implemented by nmda receptors

Eric kandel contribution

Used aplysia to demonstrate molecular basis of short and long term memory identified serotonin, PKA, CREB cascade

Ramon y cajal

neuron doctrine, neurons are discrete cells communicating at synapses

Camillo Golgi

developed the Golgi stain (silver stain) for visualizing individual neurons

Ca2+ originates from

Both intra and extracellular sources

Most protein kinases are

Important neuronal regulators

Ca2+ triggers

Presynaptic vesicle fusion and neurotransmitter release

What makes aplysia practical

Large identifiable neurons

LTP

Lasting increase in synaptic strength supporting learning and memory

Hippocampus is located where and dedicated to what, part of what

Located in temporal lobe, dedicated to declarative memory, part of the limbic system

Glutamate mediates

Ltp in hippocampus

AMPA + NMDA receptors

Primary glutamate receptors in ltp

Mg2+ blocks what at resting membrane potential

Mg2+

What removes the mg2+ block

Postsynaptic Depolarization

AMPA receptors mediate

fast excitatory transmission at most synapses in the CNS.

AMPA receptors are incorporated into

Postsynaptic membrane during ltp

Ca2+ influx through nmda receptors characterizes what

Hebb synapses

Dendritic spine density increases with

Ltp