Electrical vs Chemical Synapses

• Electrical synapses do not use neurotransmitters.

Gap Junctions

• Electrical synapses use gap junctions, which are multi-protein structures, directly connecting two neuronal membranes.
• A gap junction contains two connexon units, each made of six connexin proteins.
• Gap junctions facilitate the direct flow of ions from cell to cell.
• Electrical synapses enable fast cell-to-cell conduction and synchronization of activity between cells.

Chemical Synapses

• Chemical synapses: chemical synapses use neurotransmitters, located at the axon terminal, when voltage-gated Ca2+ channels trigger the release of neurotransmitters from synaptic vesicles into the synaptic cleft.
• Advantages of chemical synapses include excitatory and inhibitory effects.
• Chemical synapses can mediate immediate and long-term effects.
• Immediate effects involve ligand-gated ion channels, known as ionotropic receptors.
• Long-term effects involve G-protein-coupled receptors, known as metabotropic receptors.
• G-proteins inside the cell can alter ion channel functions and initiate a second messenger cascade.

Neurotransmitters and Receptors (General)

• Neurotransmitters are used in the brain, spinal cord, and peripheral nervous system for communication with muscles and internal organs.
• Different receptors respond diversely to the same neurotransmitter.
• Some ligand-gated (ionotropic) receptor channels allow Na+ or Ca2+ ions into the cell, causing depolarization and excitatory post-synaptic potentials (EPSP).
• Other ligand-gated channels allow Cl- ions into the cell to clamp the membrane at -70 mV, or let K+ ions out to hyperpolarize it, causing inhibitory post-synaptic potentials (IPSP).
• Ligand-gated ionotropic receptors cause immediate, local changes in membrane potential that are short-lived.
• G-protein coupled metabotropic receptors initiate changes inside the cell, making it more or less excitable.
• Agonists mimic neurotransmitters, while antagonists block them.

GABA (Gamma-Aminobutyric Acid)

• GABA is almost always inhibitory.
• GABAergic transmission involves ligand-gated Cl- channels (ionotropic) that let Cl- into the cell, clamping the membrane at -70 mV and causing IPSP. This configuration is widespread throughout the brain.
• GABA also includes G-protein coupled receptors (metabotropic) that increase K+ flow out of the cell and block Ca2+ flow, leading to long-lasting inhibition and are found in the thalamus and cerebral cortex.
• Low GABA levels are associated with anxiety, schizophrenia, and epilepsy.
• Ionotropic GABA receptor agonists include barbiturates (treat seizures), benzodiazepines (treat anxiety), and hypnotics (treat insomnia).
• Metabotropic GABA receptor agonist propofol is used for anesthesia.

Glutamate

• Glutamate is almost always excitatory.
• Glutaminergic transmission includes AMPA receptors, which are ionotropic ligand-gated channels. Allowing the entry of large amounts of Na+ into the cell and small amounts of K+ out of the cell, and depolarization. AMPA receptors are widespread throughout the brain.
• NDMA Receptor: NMDA receptors are simultaneously ligand-gated and voltage-gated channels that open when glutamate binds and the membrane is depolarized via AMPA receptors; wide-spread throughout the brain. The need for simultaneous stimulation allows for synaptic integration, playing a key role in learning.
• Excess glutaminergic transmission causes excitotoxicity, apoptosis, neurodegeneration, aneurysms.

Key Information About Dopamine

• Dopamine (DA) can be excitatory or inhibitory, depending on the receptor type.
• It's produced in subcortical structures that project to the prefrontal cortex, substantia nigra, ventral tegmental area of the midbrain, and nucleus accumbens.
• Dopamine is a neuromodulator with long-lasting effects, regulating reward-seeking behavior and motor control
• It plays roles in ADHD, addictive behaviors, mood disturbances, and excess is linked to psychosis and schizophrenia.

Information About Acetylcholine

• Acetylcholine (ACh) is mostly excitatory, but can be inhibitory depending on the receptor.
• It is primarily produced in the brain stem (mesopontine tegmental area) and basal forebrain (medial septal nuclei and nucleus basalis of Meynert), with projections throughout the brain.
• Acetylcholine has local and wide-spread effects, involved in attention, learning, memory, synaptic plasticity, sleep regulation, and motor functions.
• Lack of acetylcholine is linked to memory loss in neurodegenerative disorders.

Key Facts About Serotonin

• Serotonin (5-HT) can be excitatory or inhibitory, depending on the receptor type
• Serotonin is produced in the Raphe nuclei of the medulla and pons
• Serotonin is a neuromodulator with lasting effects in the brain.
• It is produced in the brain stem and released in many locations throughout the brain.
• Serotonin is involved in sleep, sex, hunger, thermoregulation, pain, cognitive functions, and learning.

Key Information About Norepinephrine

• Norepinephrine (NE) can be excitatory or inhibitory depending on the receptor type.
• Norepinephrine is a neuromodulator with wide-spread, long-lasting effects.
• It’s produced in the locus coeruleus of the pons of the brain stem.
• Norepinephrine is involved in stress response, alertness, arousal, attention, memory, and emotional regulation, with lack of norepinephrine related to ADHD.
• Brainstem nuclei producing Ach, DA, and 5-HT are known as the Ascending Reticular Activating System (ARAS) and contribute to levels of alertness and sleep.