Physiological Psych Test 2

synaptic transmission

an electrochemical process through which neurons communicate using chemical messengers (neurotransmitters)

signal transduction (step 1 of synaptic transmission)

dendrites receive graded postsynaptic potentials (ESPS or ISPS)

integration (step 2 of synaptic transmission)

temporal and spatial summation at the axon hillock determine whether the membrane potential reaches threshold to generate an action potential

propagation (step 3 of synaptic transmission)

an action potential (rapid depolarization followed by hyperpolarization) propagates down the axon

calcium influx (step 4 of synaptic transmission)

arrival of the action potential at the axon terminal triggers the opening of voltage gated calcium (Ca2+) channels, allowing Ca2+ ions to enter the terminal

Vesicle Exocytosis (step 5 of synaptic transmission)

Ca2+ entry causes synaptic vesicles to fuse with the presynaptic membrane, releasing neurotransmitter molecules into the synaptic cleft

Receptor binding (step 6 of synaptic transmission)

neurotransmitters cross the cleft and bind to specific postsynaptic receptors, opening or closing ion channels

postsynaptic potential (step 7 of synaptic transmission)

ion flow generates a local EPSP or IPSP in the postsynaptic cell

Inactivation/Clearance (step 8 of synaptic transmission)

transmission is terminated when neurotransmitters are degraded by enzymes cleared by transporters (reuptake into glia or neurons), or diffuse away

autoreceptor feedback (step 9 of synaptic transmission)

released neurotransmitters may bind to presynaptic autoreceptors to regulate further synthesis and release

small-molecule transmitters

ammino acids, monoamines, quaternary amines

small-molecule neurotransmitters synthesis site

cytoplasm of the axon terminal (enzymes made in soma)

small-molecule neurotransmitters packaging

small clear synaptic vesicles

small-molecule neurotransmitters release trigger

released by a single action potentials (Ca2+ influx)

small-molecule neurotransmitters co-existence

co-exist with other small molecules or peptides

large-molecule transmitters (neuropeptides)

opioid peptides, other neuropeptides

large-molecule transmitters (neuropeptides), synthesis site

soma/cell body (transcription and translation)

large-molecule transmitters (neuropeptides), packaging

large dense-core vesicles

large-molecule transmitters (neuropeptides) transport

microtubular axonal transport via kinesin

large-molecule transmitters (neuropeptides) release trigger

released gradually in response to repetitive action potentials

large-molecule transmitters (neuropeptides) co-existence

co-released as neuromodulators to alter classic NT actions

glutamate class/type

• class - small molecule neurotransmitter

• subtype - amino acid (primary excitatory neurotransmitter of the CNS)

glutamate synthesis and precursor materials

• precursor - glutamine (recycled from glia) or metabolic intermediates

• enzymatic process - synthesized in the cytoplasm of presynaptic terminals by metabolic enzymes. in the glutamate-glutamine cycle, astrocytes convert uptaken glutamate into glutamine via the enzyme glutamine synthase, which is then transferred back to neurons to synthesize glutamate

glutamate site of synthesis/nuclei

synthesized locally in the axon terminals of glutamatergic neurons located ubiquitously throughout the entire brain and spinal cord

glutamate major brain pathways

• cortex—cortex: intracortical connections regulating high-level processing

• cortex to basal ganglia - corticostriatal projections modulating motor initiation and cognitive control

• cortex and thalamus loop - reciprocal connections between the thalamus and cerebral cortex regulating sensory processing and state of arousal

glutamate functions

primary driver of neural excitation the CNS, mediates synaptic plasticity, long-term potentiation (LTP), learning, and memory function

AMPA Receptor

ionotropic glutamate receptor - controls a sodium (Na+) channel; mediates fast EPSPs. AMPA receptor activation depolarizes the postsynaptic membrane to activate NMDA receptors

NMDA Receptor

ionotropic glutamate receptor - permits passage of both sodium (Na+) and calcium (Ca2+). At resting potentials, its channel is physically blocked by a magnesium (Mg2+) ion. Unblocking requires dual activation: simultaneous binding of glutamate and glycine (co-agonist), along with partial membrane depolarization to electrostatically expel the Mg2+

Kainate receptor

ionotropic glutamate receptor - controls a sodium (Na+) channel; mediates fast EPSPs

mGluRs

metabotropic glutamate receptors - G-protein-coupled receptors comprising at least 8 distinct subtypes. Some function as presynaptic auto receptors to inhibit further glutamate release

Glutamate transporters

cleared from the synaptic cleft via Excitatory Amino Acid Transporters (EAATs) located on astrocytes (EAAT1, EAAT2), presynaptic neurons, and postsynaptic neurons (EAAT3, EAAT4)

glutamate enzymatic degredation

after being taken up into astrocytes, it is converted into inactive glutamine by the enzyme glutamine synthase

Phencyclidine (PCP) - glutamate

acts as an open-channel blocker (non-competitive antagonist) by binding to a specific site inside the NMDA receptor’s ion channel

cocaine interaction - glutamate

disruption or knockout of metabotropic glutamate autoreceptors (mGluR2) increases baseline extracellular glutamate levels, decreasing Nr2B- NMDA expression and enhancing cocaine-induced dopamine/glutamate release, reward sensitivity, and relapse behaviors

GABA subtype

• class - small-molecule neurotransmitter

• subtype - amino acid (primary inhibitory neurotransmitter of the brain)

GABA synthesis and precursor materials

• precursor - L-Glutamic acid (glutamate)

• enzymatic process - synthesized directly from glutamate in a single step catalyzed by the enzyme Glutamic acid decarboxylase (GAD) in the cytoplasm

GABA site of synthesis

synthesized locally in GABAergic projection neurons and local circuit interneurons throughout the forebrain, midbrain and hindbrain

GABA major brain pathways

broadly distributed throughout the central nervous system via dense networks of local interneurons and long-range projections connecting the frontal cortex, nucleus accumbens, amygdala, hippocampus, olfactory bulb, basal ganglia, and cerebellum

GABA functions

essential for preventing over-excitation across neural networks; maintains overall brain stability and signal-to-noise ratio. Regulates anxiety, muscle tone, motor control and cortical synchronization

GABAa receptor

ionotropic receptor controlling an integral chloride (Cl-) channel. Activation causes Cl- influx, resulting in rapid hyperpolarization (IPSP). Contains at least 5 distinct binding domains:

• GABA binding site

• benzodiazepine site

• barbiturate (and alcohol) site

• steroid site

• picrotoxin site

GABAb receptor

metabotropic G-protein-coupled receptor. Activation leads to the opening of potassium (K+) channels, producing a slow, long-lasting hyperpolarizing outward K+ efflux

GABAc receptor

ionotropic receptor controlling a chloride (Cl-) channel; prominently expressed in retina tissue

GABA clearance methods

removed from synaptic cleft by GABA transporters (GAT) located on both presynaptic neurons and surrounding astrocytes. or Enzymatic degradation - intracellularly metabolized in the cytoplasm of neurons and glia by GABA aminotransferase (GABA -T)

Benzodiazepines, Barbituates and Alcohol

positive allosteric modulators that bind to distinct non-GABA binding sites on the GABAa receptor, enhancing Cl- channel opening and increasing neural inhibition

Picrotoxin

binds to site on GABAa receptor as a channel blocker/antagonist, inducing convulsions

Tetanus Toxin

bacterial toxin that inhibits the presynaptic release of GABA (and glycine), causing spastic paralysis

glycine (gly) class/type

class - small-molecule neurotransmitter

subtype - amino acid (primary inhibitory neurotransmitter in the spinal cord and brainstem)

glycine synthesis/precursor molecules

metabolic amino acid precursors synthesized in the cytoplasm via local enzymatic pathway

glycine site of synthesis

synthesized in local inhibitory interneurons within the spinal cord, lower brainstem, and retina

glycine major brain pathways

concentrated in descending spinal cord motor circuits, brainstem sensory/motor relay networks and retina local circuits. Co-transmission: often co-released with GABA from the same axon terminals, generating bipartite responses (rapid IPSPs via ionotropic glycine receptors combined with sustained IPSPs via metabotropic GABAb receptors)

GABA functions

• mediates spinal inhibition, spinal reflexes, and motor movement coordination

• functions as an obligatory co-agonist at the excitatory NMDA glutamate receptor site

Ionotropic Glycine Receptor

ligand-gated chloride (Cl-) channel; activation drives Cl- inlux to produce rapid hyperpolarization (IPSPs)

NMDA glycine binding site

allosteric co-agonist site required for NMDA glutamate receptor activation

glycine synaptic clearance methods

reuptake from the cleft into presynaptic terminals and astrocytes via glycine transporters (GlyT1). or Enzymatic degradation intracellularly by the glycine cleavage system

strychnine

potent competitive antagonist that selectively blocks ionotropic glycine receptors, uninhibited spinal excitation, muscle spasms, and convulsions

tetanus toxin

blocks presynaptic release of glycine and GABA

Acetylcholine (ACh)

• class - small-molecule neurotransmitter

• subtype - quaternary amine (the first neurotransmitter identified), cells using this neurotransmitter are called cholinergic

ACh synthesis

precursors - Acetyl coenzyme A (Acetyl CoA, derrived from cellular metabolism) + Choline (derived from dietary sources and metabolic recycling)

enzymatic process - synthesized in the axon terminal cytoplasm by the enzyme choline acetyltransferase (ChAT)

ACh synthesis - Basal forebrain cholinergic system

nucleus basalis of Meynert, medial septal nucleus and nucleus of the diagonal band

ACh synthesis - Pons/Midbrain Cholinergic System

pedunculopontine nucleus, laterodorsal tegmental nucleus

ACh synthesis - somatic and autonomic motor neurons

spinal cord ventral horn motor neurons and cranial nerve motor nuclei

Basal Forebrain to Cortex

projections from the nucleus basalis innervate the entire cerebral cortex (ACh)

Septohippocampal pathway

projections from the medial septal nucleus and diagonal band project via the fornix into the hippocampal formation (ACh)

Pontine Projections

pedunculopontine and laterodorsal tegmental nuclei project to the thalamus, brainstem, and cerebellum (ACh)

ACh in the somatic system

somatic motor neurons project directly to skeletal muscle motor endplates at the neuromuscular junction (NMJ)

ACh in the Autonomic Nervous system (ANS)

preganglionic neurons in both sympathetic and parasympathetic branches release ACh onto nicotinic receptors. Postganglionic parasympathetic neurons release ACh directly onto cardiac and visceral target tissue muscarinic receptors

ACh functions

• facilitates cortical activation, attentional control, and learning

• drives hippocampal rhythms and formation of declarative memories (widespread loss of cholinergic neurons is a hallmark of Alzheimer’s disease)

• regulates REM sleep states

• Executes motor actions by triggering muscle fiber contractions at the NMJ

• mediates autonomic parasympathetic rest-and-digest responses

Nicotinic ACh Receptors (nAChR)

ionotropic receptors controlling cation channels that allow influx of NA+ (and sometimes Ca2+) and efflux of K+. Produces fast, excitatory responses. Expressed throughout the CNS, autonomic ganglia, and skeletal muscle NMJ

Muscarinic ACh receptors (mAChR)

G-protein-coupled (metabotropic) receptors (M1 through M5). Slower onset; expressed in the CNS and parasympathetic target tissues:

• excitatory subtypes - M1, M3, M5

• inhibitory subtypes - M2, M4

ACh enzymatic degredation

rapidly broken down in the synaptic cleft by the extracellular membrane-bound enzyme Acetylcholinesterase (AChE)

ACh reuptake

the liberated choline is transported back into the presynaptic terminal via high-affinity choline transporters to be reused for ACh synthesis

Curare

competitive antagonist at nicotinic ACh receptor located at the NMJ; prevents depolarization and causes flaccid paralysis

Dopamine (DA)

class - small molecule neurotransmitter

subtype - monoamine/catecholamine

Dopamine precursors

phenylalanine (dietary) → L-tyrosine → L-DOPA → Dopamine

Dopamine enzymatic pathway

Tyrosine → tyrosine hydroxylase (rate-limiting) → L-DOPA → Aromatic L-amino acid Decarboxylase → Dopamine

Dopamine site of synthesis

substantia nigra (SN) - Pars compacta in the midbrain

ventral tegmental area (VTA) - in the midbrain

Nigrostriatal (mesostriatal) pathway (dopamine)

substantia nigra projecting to the striatum (caudate nucleus and putamen). Critical component of the basal ganglia-thalamo-cortical loop

Mesolimbocortical pathway (dopamine)

originates in teh VTA and splits into two distinct projections:

• mesolimbic pathway - VTA projecting to the nucleus accumbens (NAc), amygdala, and hippocampus

• Mesocortical pathway - VTA projecting directly to the cerebral cortex, particularly the prefrontal cortex (PFC) and insula

Nigrostriatal pathway (dopamine)

controls motor initiation, execution, and inhibition. Degeneration of this pathway leads to Parkinson’s disease (PD), a basal ganglia circuit disorder

Mesolimbic Pathway (Dopamine)

mediates reinforcement, incentive salience, reward processing, and pleasure

Mesocortical pathway (dopamine)

regulates prefrontal executive functions, including working memory, planning, problem solving and attentional focus

All dopamine receptors are

G-protein-coupled (metabotropic) receptors categorized in 5 subtypes (D1-D5)

D1 - like family (D1, D5) - Dopamine

couples to Gs proteins; stimulates adenylyl cyclase; produces excitatory postsynaptic responses

D2 - like family (D2, D3, D4) - Dopamine

couples to Gi proteins; inhibits adenylyl cyclase; produces inhibitory postsynaptic responses. Function both pre and post synoptically (as auto receptors that decrease further dopamine synthesis and release)

Dopamine transporters

primary clearance via the presynaptic dopamine transporter (DAT)

Monoamine Oxidase (MAO)

degrades dopamine - intracellular enzyme (located in cytoplasm/mitochondria) that breaks down monoamines

Catechol-O-Methyltransferase (COMT)

degrades dopamine - cleaves catecholamines in the synaptic space or cytoplasm prior to/following reuptake

Apomorphine

Biphasic dopamine receptor agonist

• at low does - selectively binds presynaptic D2 auto receptors with high affinity, suppressing dopamine production (acts functionally as an antagonist)

• at high doses - activates postsynaptic dopamine receptors directly (acts as a postsynaptic agonist)

cocaine

blocks DAT, inhibiting reuptake and elevating extracellular dopamine in the nucleus accumbens to reinforce addictive drug behaviors

Norepinephrine (NE/Noradrenaline)

class - small-molecule neurotransmitter

subtype - monoamine/catecholamine (cells synthesizing NE are termed noradrenergic)

NE precursor pathway

L-Tyrosine → L-DOPA → Dopamine → norepinephrine

NE enzymatic process

synthesized from dopamine within synaptic vesicles via the enzyme dopamine hydroxylase

Locus coeruleus (Blue spot)

dense noradrenergic nucleus located in the dorsal pons (leads to NE)

lateral tegmental area

noradrenergic cell groups scattered in the midbrain tegmentum (leads to NE production)

Central Projections (NE)

Locus coeruleus neurons project diffusely to the cerebral cortex, hippocampus, basal ganglia, thalamus, cerebellum, and spinal cord

Non-synaptic transmission

NE is frequently released from axonal varicosities - periodic swellings along the axon-length — allowing diffuse “volume transmission” into the extracellular space

Peripheral Nervous System Pathways (NE)

released by postganglionic sympathetic nerve fibers onto visceral effector organs, and secreted directly into the bloodstream as a hormone by the adrenal medulla

Norepinephrine functions

• increases behavioral vigilance, environmental attentiveness, arousal, and cognitive readiness

• mediates central control of appetite, mood, and sexual behavior

• orchestrates peripheral sympathetic fight-or-flight physiological responses (e.g., pupil dilation, heart rate acceleration, airway relaxation, glucose release)

all noradrenergic receptors are

G-protein-coupled (metabotropic) adrenergic receptors responsive to both NE and epinephrine