Neuropsychopharmacology - Glutamate & Gaba

Front 1

Open Na or Ca channels tend to

Back 1

Depolarize neurons (EPSP)

Front 2

Open K channels tend to

Back 2

Hyperpolarize neurons (IPSPs)

Front 3

Open Cl channels usually cause

Back 3

IPSPs

Front 4

What is the most important excitatory NT in the brain and the primary NT for fast chemical signalling between cells?

Back 4

Glutamate

Front 5

How many neurons have receptors for glutamate?

Back 5

Approximately all receptors

Front 6

What appears to be a major mechanisms for learning and memory?

Back 6

Changes in glutamate signaling

Front 7

What produces excitoxicity?

Back 7

Excessive extracellular glutamate

Front 8

Glutamine is synthesized to Glutamate by which enzyme?

Back 8

Glutaminase

Front 9

How is glutamate transmitted?

Back 9

vGLUTs package glutamate into vesicles and EAATs take up glutamate from synaptic cleft where it is taken back to the terminals

Front 10

Where do you find vGLUT2 mRNA?

Back 10

The inferior colliculus, thalamus, and deep cerebellar nuclei.

Front 11

Where would you find vGLUT1 mRNA?

Back 11

In the cerebellar cortex, hippocampus, and cortex

Front 12

Where is vGLUT3?

Back 12

Expressed in some other neuron types

Front 13

What type of receptors are glutamate receptors?

Back 13

They are both ionotropic and metabotropic and both are found presynaptically and postsynaptically.

Front 14

What are the 3 kinds of iGluRs?

Back 14

AMPA, Kainate, & NMDA which are all compromised of multiple subunits, encoded by different genes and subject to splice variation

Front 15

What ions do the iGluRs allow through?

Back 15

Na++ and NMDA also allows Ca++

Front 16

Steps of fast synaptic transmission

Back 16

Action potential opens Na++ channels and causes depolarization, which causes the opening of Ca++ channels. Ca++ elevation occurs in microdomain and binds to synaptotagmin which causes opening of fusion pore. Glutamate then passes through fusion pore and diffuses in to the cleft. The opening of AMPA channels generates EPSC

Front 17

Why is the NMDA receptor a molecular coincidence detector?

Back 17

It is ligand-gated and also voltage-gated. It is normally blocked by Mg but a depolarization relieves blockade. The entry of Ca++ thus depends on glutamate in synaptic cleft and a postsynaptic depolarization.

Front 18

What is LTP?

Back 18

Persistent changes in glutamate signalling - widely believed to underlie learning and memory.

Front 19

What does LTP result from?

Back 19

Altered presynaptic release of glutamate or altered postsynpatic receptor signalling, or both.

Front 20

What role do NMDA receptors have in LTP?

Back 20

Typically involved in induction, not expression of LTP.

Front 21

What is spike-timing-dependent plasticity?

Back 21

Synaptic plasticity depends on the relative timing of presynaptic/postsynaptic depolarization.

Front 22

LTP vs. LTD

Back 22

if presynaptic activity precedes postsynaptic spike, you get LTP. if presynaptic acitivty follows postsynaptic spike, you get LTD.

Front 23

What are metabotropic glutamate receptors?

Back 23

8 main types that are all GPC, divided into 3 groups by structure and activity type:

Front 24

What roles do the metabotropic glutamate receptors play?

Back 24

Modulation of other receptors and participation in synaptic plasticity.

Front 25

What is GABA?

Back 25

Most important inhibitory NT in the adult, vertebrate brain that is found throughout the brain in high concentrations and synthesized from glutamate.

Front 26

How is GABA synthesized?

Back 26

Glutamate is synthesized by GAD (glutamic acid decarboxylase)

Front 27

How is GABA transmitted?

Back 27

Synthesized GABA is placed in vesicles by vGAT, a GABA transporter. It is released into synaptic cleft, then taken up by GABA transporters 1,2,3 on both neurons and glia cells.

Front 28

What two types of GABA receptors are there?

Back 28

GABAa receptors are ionotropic (ligand-gated Cl channels) and GABAb receptors are metabotropic (G-protein-coupled)

Front 29

What is the makeup of GABAa receptors?

Back 29

Consists of 5 subunits that surround a central pore (Cl channel). Most have 2 alpha, 2 beta, and one gamma/sigma

Front 30

Where are GABAa receptors located?

Back 30

Different neurons express different combination's of GABAa subunits. Even on the same neuron, different combinations are found on different locations.

Front 31

What type of receptors are GABAb?

Back 31

They are obligate heterodimers - that is, they require both GABAb1 and b2 for functionality. They are G-protein coupled

Front 32

G-alpha i function

Back 32

Inhibits adenylate cyclase.

Front 33

G-beta gammam function

Back 33

Modulates potassium and calcium ion channels.

Front 34

What is the relationship between EPSPs and IPSPs and whether or not a neuron will spike or not?

Back 34

A EPSP can cause threshold of activation which triggers an action potential. A IPSP can counteract an EPSP resulting in no threshold of activation and no action potential.

Front 35

What do IPSP and EPSPs do in awake, alert brains?

Back 35

Both inputs are carefully balanced so neurons stay close to firing threshold most of the time.

Front 36

Projection cells vs. interneurons

Back 36

In most parts of the brain, the main projection cells are spiny glutamatergic neurons, and the main interneurons are GABAergic aspiny neurons.

Front 37

What is the makeup of the microcircuitry within the cerebral cortex?

Back 37

80% of cortical neurons are excitatory glutamatergic - mostly spiny,pyramidal cells, while 20% are inhibitory GABAergic interneurons.

Front 38

What does it mean to say synaptic weights adjust to balance excitation and inhibition?

Back 38

There is feedback connections between neurons - one cell projects to 2 other cells, that project back onto it.

Front 39

What produces seizures?

Back 39

Blocking GABA transmission in vivo

Front 40

What are pyramidal cells?

Back 40

The main information-bearing nodes of cortical networks.

Front 41

How do interneurons control microcircuit dynamics?

Back 41

There are many distinct types of interneruons that act to adjust network dynamics.

Front 42

What is the current best candidate for a "lesion" in schizophrenia?

Back 42

Specific deficit in prefrontal cortex axo-axonic interneurons.

Front 43

What are the 3 major stages of sleep-wake cycle?

Back 43

Awake, slow-wave sleep, and REM sleep

Front 44

Awake cycle

Back 44

desynchronized EEG. low-amplitude, brief bursts of high frequencies

Front 45

Slow-wave sleep

Back 45

Large amplitude, low frequencies

Front 46

REM sleep

Back 46

Rapid-eye movement; dreaming. EEG resembles awake state but loss of muscle tone

Front 47

How do interneurons orchestrate synchronous neural activity?

Back 47

Different classes of hippocampal GABAergic interneurons are active at different phases of each rhythm and can pace activity in the rest of the cells.

Front 48

What are the importance of cell assemblies?

Back 48

They are a group of neurons that fire together to convey information to other cells.