Action Potentials and Synapses

• Electrical changes in neurons, known as action potentials, are triggered by stimuli that depolarize the membrane once a threshold is reached.
• Temporary changes in cell membrane voltage can result from environmental stimuli or neuronal interactions.
• These changes are called graded potentials and they influence the likelihood of action potential generation.
• Slight temperature change in water can create varying graded potentials

Summation of Graded Potentials

• Graded potentials can be depolarizing (increasing voltage) or hyperpolarizing (decreasing voltage).
• The summation of graded potentials can be spatial (multiple inputs at different locations) or temporal (multiple signals from the same input over time).
• If the sum of graded potentials leads to a change of +15 mV from -70 mV to -55 mV, the neuron can reach threshold.

Types of Synapses

• Neurons communicate through chemical and electrical synapses.
• Chemical synapses use neurotransmitter release (e.g., at the neuromuscular junction).
• The presynaptic neuron releases neurotransmitters that cross the synaptic cleft to bind with specific receptors on the postsynaptic neuron.
• Each synapse has defined characteristics, including presynaptic elements, neurotransmitter types, synaptic cleft presence, and receptor interactions.

Neurotransmitter Systems

• "Cholinergic" neurotransmitter systems are based on acetylcholine.
• Cholinergic receptors include nicotinic and muscarinic, which bind to specific drugs and neurotransmitters.
• Other neurotransmitters, like amino acids (glutamate, GABA, glycine), form their unique systems with respective receptors, which are reabsorbed after functioning.
• Biogenic amines, derived from amino acids (e.g., serotonin from tryptophan), also feature distinct receptor systems and undergo reuptake for recycling.

Action of Neurotransmitters

• Action potentials reaching axon terminals open voltage-gated Ca2+ channels, increasing intracellular calcium.
• Calcium influx facilitates neurotransmitter vesicles merging with the presynaptic membrane to release neurotransmitters into the synaptic cleft via exocytosis.
• Binding of neurotransmitters to their receptors on the postsynaptic membrane initiates a response, which can be either excitatory or inhibitory.

Neurotransmitters and Their Systems

• Amines such as dopamine, adrenaline (epinephrine), and noradrenaline (norepinephrine) are derived from the amino acid tyrosine.
• Dopamine operates within the dopaminergic system, featuring dopamine receptors that are cleared from the synapse by transport proteins in the presynaptic cell membrane.
• Noradrenaline and adrenaline belong to the adrenergic neurotransmitter system, binding to alpha and beta receptors, and are reabsorbed into the presynaptic neuron.
• The adrenal gland produces and releases adrenaline and noradrenaline into the bloodstream as hormones.
• Neuropeptides are neurotransmitters formed from amino acid chains linked by peptide bonds.
• Met-enkephalin is a neuropeptide 5 amino acids long, while beta-endorphin comprises 31 amino acids.

Receptors and Their Effects

• The impact of neurotransmitters on postsynaptic elements depends on the presence and type of receptor proteins present.
• Acetylcholine binding to nicotinic receptors causes depolarization due to Na+ influx.
• Acetylcholine binding to muscarinic receptors may result in either depolarization or hyperpolarization based on receptor subtype.
• Amino acid neurotransmitters like glutamate (excitatory) cause depolarization, while glycine and GABA (both inhibitory) induce hyperpolarization.
• Biogenic amines can exhibit mixed effects: D1 receptors (dopamine) lead to depolarization, whereas D2-type receptors cause hyperpolarization.
• Receptor activation can also influence gene transcription and metabolic processes within neurons.

Signal Transduction Mechanisms

• Neurotransmitters bind to either ionotropic receptors (ligand-gated ion channels) or metabotropic receptors (engage a complex of proteins to initiate metabolic changes).
• In metabotropic signalling, neurotransmitters act as first messengers, triggering G protein activation that leads to the production of second messengers such as cyclic adenosine monophosphate (cAMP) and inositol triphosphate (IP3).
• These second messengers mediate various intracellular processes, often modifying ion channel activity or influencing gene expression.

Neurodegenerative Diseases and Proteopathy

• Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are linked to proteopathy—the harmful accumulation of misfolded proteins.
• Alzheimer's is characterized by the buildup of beta-amyloid plaques.
• Parkinson’s involves toxic accumulation of alpha-synuclein in the substantia nigra.
• Proper protein function hinges on correct three-dimensional folding; disturbances can lead to protein misfolding and toxic accumulation.
• Prevent accumulation and address the diseases at the production level within cells.

Neural Communication and Action Potentials

• The action potential is the foundational electrical signal in neurons that propagates along axons.
• Action potentials are initiated by external stimuli or input from other neurons.
• Incoming stimuli cause ion channels to open, resulting in graded potentials, which can be depolarizing or hyperpolarizing.
• Graded potentials influence the likelihood of reaching the action potential threshold.
• Generator potentials arise from sensory neuron dendrites.
• Receptor potentials come from specialized sensory cells.
• Postsynaptic potentials (PSPs) stem from neuron-neuron interactions.
• Synaptic transmission primarily occurs via chemical synapses, where neurotransmitters released from presynaptic neurons affect postsynaptic receptors, necessitating neurotransmitter removal to limit signaling duration.

Neurotransmitter Systems and Characteristics

• Various neurotransmitter systems exhibit specific characteristics, such as reuptake mechanisms.
• Neurotransmitter systems are subject to degradation by enzymes, and the neurotransmitters exhibit diverse potential effects (e.g., excitatory or inhibitory).
• The cholinergic system operates at the neuromuscular junction and throughout the nervous system.
• Neurotransmitters include amino acids like glutamate, glycine, and GABA.
• Neuropeptides and biogenic amines contribute to varied synaptic functions and responses.