Chapter 8 - Organization and Function of GABA

GABA Interneurons

Cortex and Hippocampus neurons

GABA Projection neurons

Striatum and Cerebellar Purkinje Cells

Spinocerebellar Ataxias

Rare genetic mutation that causes degeneration and death of Purkinje cells

Causes ataxia, impaired balance, and poor motor coordination

GABA(A) receptors

Ionotropic Receptor

Composed of 5 subunits

allows Cl- to move into the cell, causing hyperpolarization and inhibition

Activates more when the membrane was previously depolarized
Responds to low levels of GABA

Mild, tonic hyperpolerization

Muscimol (from Amanita Muscaria)

GABA(A) agonist that comes from a mushroom

High doses causes intoxication characterized by hyperthermia, pupil dilation, mood elevation, difficulties in concentration, ect ect ect

SIMILAR TO LCD

Benzodiazepines, Barbituates, and Ethanol, Neurosteroids, Anesthetics

GABA(A) receptors are sensitive to CNS-depressant drugs

they act as positive allosteric modulators, which can lead to tolerance, dependence, and withdrawl symptoms when drug treatment is terminated

Anethestics

Increases inhibitory receptors

Can decrease excitatory receptors depending on the anethestics

Catamenial Epilepsy

roughly 40-60% of women suffer

Neurosteroids, particularly ALLO, may be involved

TYPE I Catamenial Epilepsy

Estrogen/Progesterone is high during periovulatory period

During Ovulation period

Type II Catamenial Epilepsy

Withdrawal from diminishing diminishing progesterone (after luteal phase)

Postpartum depression

Major depressive disorder, ALLO alleviates postpartum depression

Better treatment then SSRI’s

Status Epilepticus

CL- leaves instead of enters when GABA binds

No amount of time for brain to recover between seizures

Drugs that targets BDZ-insensitive extrasynaptic GABAA receptors is treatment

GABA(B) receptors

Metabotropic receptors

Postsynaptic GABA(B) receptors

Inhibits neuronal firings by stimulate K+ Channel opening

inhibits cAMP

Presynaptic GABA(B) receptors

Acts as autoreceptors or heteroreceptors and inhibits Ca2+ channels from opening

Inhibits cAMP