Synaptic Transmission, Receptors, Second Messengers, and Memory Mechanisms

Comprehensive vocabulary flashcards covering the cellular and molecular mechanisms of synaptic transmission, ionotropic and metabotropic neurotransmitter receptors, second messenger cascades, protein kinases and phosphatases, optogenetics, chemogenetics, and the neurobiology of learning and memory.

Electrical Synapse

A specialized junction where current flows directly from one neuron to another via gap junctions, typically allowing bidirectional transmission without synaptic delay.

Connexon

A hexameric channel complex formed by six connexin protein subunits; two aligned connexons from adjacent plasma membranes form an intercellular gap junction channel.

Otto Loewi's Experiment

A landmark experiment demonstrating chemical transmission where stimulating the vagus nerve of an isolated frog heart slowed its beating, and transferring the perfusate solution to a second denervated heart produced the identical inhibitory slowing.

Active Zone

The specialized region of the presynaptic plasma membrane where synaptic vesicles dock and fuse to release neurotransmitters, rich in voltage-gated $\text{Ca}^{2+}$ channels.

Postsynaptic Density

A protein-dense specialization anchored to the postsynaptic membrane immediately opposite the active zone that clusters neurotransmitter receptors and associated signaling enzymes.

Synapsin

A protein that reversibly tethers synaptic vesicles to actin filaments in the cytoskeleton to maintain a reserve pool; phosphorylation by protein kinases causes it to dissociate from vesicles to mobilize them.

SNARE Proteins

A family of membrane-associated proteins (including v-SNARE synaptobrevin on the vesicle, and t-SNAREs syntaxin and SNAP-25 on the plasma membrane) that assemble into a four-helix bundle to drive membrane fusion.

Synaptotagmin

A vesicular calcium-sensing protein that binds $\text{Ca}^{2+}$ upon influx through voltage-gated channels, triggering rapid vesicle fusion with the presynaptic plasma membrane.

Clathrin

A triskelion-shaped protein complex that polymerizes into a curved, basket-like lattice around budded vesicular membrane during endocytosis.

Dynamin

A GTPase that polymerizes into a helical ring around the lipid stalk of a budding endocytic vesicle and pinches it off from the plasma membrane.

Excitatory Postsynaptic Potential (EPSP)

A transient depolarization of the postsynaptic membrane potential caused by neurotransmitter-induced cation influx, shifting the membrane potential closer to the action potential threshold.

Inhibitory Postsynaptic Potential (IPSP)

A transient postsynaptic hyperpolarization (or stabilization) driven by anion influx (e.g., $\text{Cl}^-$) or cation efflux (e.g., $\text{K}^+$), reducing the likelihood of action potential generation.

Reversal Potential ($E_{\text{rev}}$) Rule of Postsynaptic Action

The membrane potential at which net current through an open channel equals zero; a synapse is defined as excitatory if its $E_{\text{rev}}$ is more positive than the action potential threshold, and inhibitory if its $E_{\text{rev}}$ is more negative than threshold.

Spatial Summation

The algebraic integration of postsynaptic potentials generated simultaneously at distinct, separate synapses distributed across the dendritic tree.

Temporal Summation

The additive integration of multiple postsynaptic potentials generated at the exact same synapse in rapid succession within approximately $1\text{--}15\,\text{ms}$.

Passive Current Flow

The decremental conduction of electrical current along a neuronal membrane in the absence of regenerative action potentials, comparable to the spread of current along a leaky electrical cable.

AMPA Receptor

A tetrameric ionotropic glutamate receptor non-selectively permeable to $\text{Na}^+$ and $\text{K}^+$ with an $E_{\text{rev}}$ of $0\,\text{mV}$, whose channel gate opens via clamshell closure upon binding two or more glutamate molecules.

$\text{GABA}_{\text{A}}$ Receptor

A heteropentameric ionotropic receptor (typically composed of $2\alpha, 2\beta, 1\gamma$ subunits) selectively permeable to $\text{Cl}^-$, mediating primary fast inhibitory synaptic transmission in the brain.

Developmental Chloride Shift

The developmental transition where GABA acts as an excitatory/depolarizing neurotransmitter in immature neurons due to high intracellular $[\text{Cl}^-]$, shifting to an inhibitory/hyperpolarizing action in mature neurons as intracellular $[\text{Cl}^-]$ drops.

End Plate Potential (EPP)

The large, suprathreshold depolarization recorded at the postsynaptic motor end plate of skeletal muscle in response to an action potential in the motor axon.

Miniature End Plate Potential (MEPP)

A spontaneous, subthreshold depolarization of less than $1\,\text{mV}$ observed in the muscle end plate without presynaptic stimulation, corresponding to the quantal exocytosis of a single acetylcholine vesicle.

Synaptic Quantum

The elementary indivisible unit of neurotransmitter release, equivalent to the full chemical contents of a single presynaptic vesicle (~10,000 acetylcholine molecules at the neuromuscular junction).

Agonist

A chemical compound that binds to a neurotransmitter receptor and mimics the functional biological response produced by the endogenous neurotransmitter.

Competitive Antagonist

An agent that binds reversibly or irreversibly to the exact orthosteric binding site of a neurotransmitter, preventing receptor activation without activating it.

$\alpha$-Bungarotoxin

A peptide neurotoxin derived from the venom of the banded krait (Bungarus multicinctus) that acts as a competitive antagonist by irreversibly binding to nicotinic acetylcholine receptors and blocking ion flux.

Glycine Receptor

A pentameric ligand-gated chloride channel mediating the majority of fast inhibitory synaptic transmission in the spinal cord and brainstem.

Strychnine

A potent plant alkaloid that acts as a competitive antagonist of the ionotropic glycine receptor, causing severe convulsions and hyperexcitability by blocking chloride-mediated inhibition.

NMDA Receptor

A tetrameric ionotropic glutamate receptor permeable to $\text{Na}^+$, $\text{K}^+$, and $\text{Ca}^{2+}$ that acts as a coincidence detector requiring both glutamate binding and membrane depolarization to expel blocking $\text{Mg}^{2+}$ ions.

Heterotrimeric G-Protein

A membrane-associated signaling complex consisting of $\alpha$, $\beta$, and $\gamma$ subunits; activation by a GPCR induces exchange of GDP for GTP on the $\text{G}\alpha$ subunit and dissociation into $\text{G}\alpha\text{-GTP}$ and $\text{G}\beta\gamma$ complexes.

Muscarinic Acetylcholine Receptor

A 7-transmembrane metabotropic receptor subtype that couples via G-proteins ($\text{G}\beta\gamma$) to activate inward-rectifying $\text{K}^+$ channels, hyperpolarizing cardiac muscle cells and slowing heart rate.

$\beta$-Adrenergic Receptor

A metabotropic receptor for norepinephrine that couples to $\text{G}_s$, stimulating adenylyl cyclase to synthesize cAMP and activate protein kinase A (PKA).

$\alpha_2$-Adrenergic Receptor

A metabotropic autoreceptor coupled to $\text{G}_i$ on presynaptic noradrenergic terminals that suppresses adenylyl cyclase and inhibits voltage-gated $\text{Ca}^{2+}$ channels, reducing further transmitter exocytosis.

Tyrosine Hydroxylase (TH)

The rate-limiting biosynthetic enzyme that catalyzes the hydroxylation of L-tyrosine to L-DOPA in the catecholamine synthesis pathway.

D1 and D2 Dopamine Receptors

Metabotropic dopamine receptor subtypes; D1 couples to $\text{G}_s$ to stimulate adenylyl cyclase and elevate cAMP, whereas D2 couples to $\text{G}_i$ to inhibit adenylyl cyclase and reduce cAMP.

Class I Metabotropic Glutamate Receptors (mGluRs)

The GPCR subtype group including mGluR1 and mGluR5 that couples to $\text{G}_q$, activating phospholipase C to trigger phosphoinositide hydrolysis.

Phospholipase C (PLC)

A membrane-bound enzyme activated by $\text{G}_q$ that cleaves phosphatidylinositol 4,5-bisphosphate ($\text{PIP}_2$) into the two second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate ($\text{IP}_3$).

Inositol 1,4,5-Trisphosphate ($\text{IP}_3$) Receptor

An intracellular ligand-gated channel localized to the membrane of the endoplasmic reticulum that releases sequestered $\text{Ca}^{2+}$ into the cytosol upon binding $\text{IP}_3$.

DREADDs

Designer Receptors Exclusively Activated by Designer Drugs; genetically modified GPCRs (such as hM3Dq for excitation or hM4Di for inhibition) unresponsive to native ligands and selectively activated by synthetic drugs such as clozapine-N-oxide (CNO).

Channelrhodopsin

A light-sensitive microbial opsin that acts as an inward non-selective cation channel when illuminated by blue light, inducing rapid neuronal depolarization.

Halorhodopsin

A light-driven inward chloride ion pump that transports $\text{Cl}^-$ into neurons upon yellow/green light illumination, causing robust hyperpolarization and silencing of action potentials.

Tricyclic Antidepressants (TCAs)

A class of psychotherapeutic drugs (such as desipramine) that inhibit the presynaptic norepinephrine transporter (NET), elevating synaptic norepinephrine concentration.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Antidepressant compounds that selectively inhibit the serotonin transporter (SERT) at the presynaptic terminal, prolonging 5-HT signaling in the synaptic cleft.

Monoamine Oxidase (MAO) Inhibitors

Drugs that block the mitochondrial enzymes MAO-A and/or MAO-B, preventing the intracellular enzymatic breakdown of catecholamines and serotonin to enhance transmitter availability.

Protein Kinase A (PKA)

A heterotetrameric serine/threonine kinase consisting of two regulatory and two catalytic subunits; binding of four cyclic AMP molecules disinhibits and releases the active catalytic subunits.

Protein Kinase C (PKC)

A serine/threonine kinase whose regulatory domain is disengaged when membrane-bound diacylglycerol (DAG), calcium ions, and phosphatidylserine bind cooperatively to unleash its catalytic activity.

CaMKII Autophosphorylation

An intra-holoenzyme reaction where calcium/calmodulin binding to adjacent CaMKII subunits allows mutual phosphorylation at threonine 286 (T286), locking the kinase into an autonomous, persistently active state even after $\text{Ca}^{2+}$ levels drop.

Calcineurin (PP2B)

A calcium- and calmodulin-dependent protein phosphatase that dephosphorylates specific target substrates to counteract the actions of protein kinases.

Patient H.M.

A famous neurological patient who underwent bilateral medial temporal lobectomy (including excision of the hippocampus) to treat epilepsy, resulting in profound anterograde declarative amnesia while preserving working memory and procedural motor skill learning.

Mirror-Drawing Task

A procedural skill-learning paradigm requiring tracing a figure seen only in a mirror; Patient H.M. showed normal improvement in performance across days despite retaining no conscious, declarative memory of having performed the task.

Declarative Memory

A category of long-term memory that can be consciously recalled and articulated, subdivided into episodic memory (personal events) and semantic memory (general facts), which strictly depends on the hippocampus and medial temporal lobe structures.

Nondeclarative Memory

A broad category of unconscious, implicit long-term memory that manifests through performance rather than recollection, encompassing motor skill learning, priming, and classical conditioning.

Morris Water Maze

A behavioral task used to assess spatial learning and declarative-like navigation in rodents, who must use distal spatial room cues to locate a submerged escape platform hidden in an opaque circular pool.

Context Fear Conditioning

A behavioral paradigm where an animal learns to associate a distinctive training chamber with an aversive unconditioned stimulus (such as a footshock), assessed by measuring the duration of freezing (immobility) upon re-exposure.