Neurotransmitters Neuropeptides Amines Quaternary amines Acetylcholine ACh Monoamines

Neurotransmitters • Neuropeptides • Amines • Quaternary amines • Acetylcholine (ACh) • Monoamines • Catecholamines • Epinephrine (EPI) • Norepinephrine (NE) • Dopamine (DA) • Indoleamines • Serotonin (5 -HT) • Melatonin • Amino acids • Gamma-aminobutyric acid (GABA) • Glutamate (GLU) • Glycine • Histamine (HIST) • Opioid peptides • Enkephalins (ENK) • Endorphins (END) • Peptide Hormones • Oxytocin (Oxy) • Substance P • Cholecystokinin (CCK) • Vasopressin (ADH) • Neuropeptide Y (NPY) • Brain-derived Neurotrophic factor • Hypothalamic Releasing Hormones • Gn. RH • TRH • CRH • Lipids • Anandamide • Gases • Nitric Oxide (NO)

Glutamate Synthesis • Glutamine • Glutaminase • Glutamic Acid • Glutamate • Aspartic Acid • Aspartate

Distribution of VGLUTs

Glutamate Synapse

Glutamate Receptors • AMPA receptors • • Kainate receptors • • Glu. K 1 -5 NMDA receptors • • Glu. A 1 -4 Glu. N 1 Glu. N 2 A-C Glu. N 3 A-B Metabotropic receptors • m. Glu. R 1 -8 Iontotropic Metabotropic AMPA Receptor

All ionotropic glutamate receptor channels conduct Na+ ions into the cell

NMDA receptor properties

Types of Memory (iconic memory) (7 bits for 30 seconds)

Cellular Mechanism for Learning Hebbian Synapse: Frequent stimulation can change the efficacy of a synapse

Enrichment Protocol Impoverished Enriched

Quantifying Dendritic Arborization

Hippocampal Brain Slicing

Hippocampal Pathways

Long-Term Potentiation (LTP) each triangle represents a single action potential Slope of the EPSP (one characteristic measure of an action potential) baseline response potentiated response Hippocampus has a three synaptic pathway Stimulate one area (mossy fibers) and record the action potentials in another (CA 1) Stimulate multiple times to get a baseline response Once a stable baseline is established give a brief high frequency stimulating pulse Use the same stimulating pulse as in baseline but now see a potentiated response This potentiated response can last hours, days, or even weeks (LTP)

Normal Synaptic Transmission Glutamate Channels: NMDA Mg 2+ block no ion flow AMPA Na+ flows in depolarizes cell

LTP Induction With repeated activation the depolarization drives the Mg 2+ plug out of the NMDA channels Ca 2+ then rushes in through the NMDA channels Ca 2+ stimulates a retrograde messenger to maintain LTP Ca 2+ also stimulates CREB to activate plasticity genes

LTP-induced Neural Changes

Neurobiological Changes via Learning Dendritic changes: • Increased dendritic arborization • Increased dendritic bulbs Synaptic changes: • More neurotransmitter release • More sensitive postsynaptic area • Larger presynaptic areas • Larger postsynaptic areas • Increased interneuron modulation • More synapses formed • Increased shifts in synaptic input Physiological changes: • Long-Term Potentiation • Long-Term Depression

Learning Requires Protein Synthesis! Anisomycin: (protein synthesis inhibitor) blocks long term memory

GABA Synthesis • Glutamate • Glutamic Acid Decarboxylase (GAD) • GABA

GABA Synapse

GABA Receptors • GABAA receptors • GABAB receptors • GABAC receptors Iontotropic Metabotropic GABAA Receptor

GABAA receptor properties

Anxiety Disorders • • • feelings of concern or worry increased muscle tension restlessness impaired concentration sleep disturbances irritability increased heart rate Increased sweating other signs of “fight-or-flight” response

Three. Component Model of Anxiety • General Anxiety Disorder (GAD) • Panic Attacks • Panic Disorder • Phobias • Social Anxiety Disorder (SAD) • Posttraumatic Stress Disorder (PTSD) • Obsessive Compulsive Disorder (OCD)

Neurobiology of Anxiety

Neurobiology of Anxiety

Neurochemistry of Anxiety • Corticotropin-releasing factor (CRF) • Norepinephrine (NE) • Serotonin (5 -HT) • Dopamine (DA) • GABA

GABA and Anxiety • Benzodiazepines (BDZ) and barbiturates cause sedation and reduced anxiety by binding to modulatory sites on the GABA receptor complex • BDZ binding sites are widely distributed in the brain. • They are in high concentration in the amygdala and frontal lobe.

GABA and Anxiety • Inverse agonists bind to BDZ sites and produce actions opposite of BDZ drugs— increased anxiety, arousal, and seizures. • The β-carboline family produces extreme anxiety and panic. They are presumed to uncouple the GABA receptors from the Cl– channels so that GABA is less effective.

GABA and Anxiety • Animal studies have found that natural differences in anxiety levels are correlated with the number of BDZ binding sites in several brain areas. • PET scans of patients with panic disorder show less benzodiazepine binding in the CNS, particularly in the frontal lobe.

Drugs for Treating Anxiety • • • Anxiolytics Sedative–hypnotics Benzodiazepines Barbiturates Antidepressants

Benzodiazepines

BDZ binding and antianxiety effect

Barbiturates

Antidepressants