Excitatory and Inhibitory Neurons Overview

Excitatory and Inhibitory Neurons

• Majority (80%) of brain neurons are excitatory, prompting neighboring cells to fire.
• Pyramidal cells are common excitatory neurons in the cerebral cortex, identified by their cone-shaped cell bodies and branched dendrites (apex and base).
• Dendrites collect signals from all cortical layers.
• Axons send signals to multiple destinations.
• 20% of neurons are inhibitory, suppressing neighboring neuron activity and regulating circuit function.
• Excitatory neurons typically pass signals forward in a circuit, sending outputs to other brain parts.
• Inhibitory neurons are often local, looping responses back to the circuit's earlier segments.
• Interplay of excitatory and inhibitory signals is crucial for learning, signal tuning, and smoothing.
• Imbalances in excitatory/inhibitory neuron activity can contribute to seizure disorders like epilepsy.
• Circuits can be organized in various input structures (feed-forward inhibitory, feedback inhibition).
• Both are examples of recurrent neural networks with feedback signals between interconnected neurons.

Neurons and Glia

• Neuron is the functional unit of neural circuits and networks.
• Neurons vary in shape and size and consist of a cell body (soma), dendrites, and an axon.
• Cell body houses the nucleus and protein synthesis machinery.
• Dendrites extend from the cell body, receiving signals from other neurons at synapses.
• Axons transmit signals to other neurons, muscles, or glands; can vary in length from fractions of a centimeter to over a meter.
• Neurons are associated with support cells called glia, previously believed to outnumber neurons 10:1, however, research suggests a closer ratio of 1:1 in some brain regions.
• Various glial types exist in the central nervous system (astrocytes, microglia, ependymal cells, oligodendrocytes).
• Astrocytes regulate ion concentrations, provide nutrients, and aid new connection formation between neurons.
• Microglia are the "immune" cells, acting as phagocytes.
• Ependymal cells produce cerebrospinal fluid.
• Oligodendrocytes insulate axons with myelin.

Ion Channels and Action Potentials

• Ions cross neuron membranes through ion channels (tunnel-like proteins).
• Membrane voltage difference in resting neurons is approximately -70 mV (more negative inside).
• Signals from other neurons can depolarize (less negative) or hyperpolarize (more negative) the membrane by opening ion channels in dendrites.
• If the sum of signals reaches the threshold voltage, voltage-gated ion channels open, triggering an action potential which travels down the axon.

Synapses and Neurotransmission

• Signals move from one neuron to the next at junctions called synapses.
• Synapses consist of an axon terminal, the dendrite of a neighboring neuron, and the synaptic cleft (space in-between).
• Chemical signals (neurotransmitters) cross the synaptic cleft.
• When an action potential reaches the axon terminal, calcium ions enter the cell.
• Calcium triggers neurotransmitter release from synaptic vesicles into the synaptic cleft.
• Neurotransmitters include varied molecules like amino acids, gases, and small chemicals.
• Peptide neurotransmitters are synthesized in the cell body, packaged in vesicles (bud off from Golgi) and transported down the axon along microtubules.
• Neurotransmitters diffuse to the postsynaptic density (dendrite surface), triggering a response following binding to specific receptors.
• Multiple neuron molecules including astrocytes are important to neurotransmitter removal preventing continuous activation.

Receptors and Types

• Two types of neurotransmitter receptors on the postsynaptic membrane: ionotropic and metabotropic.
• Ionotropic receptors bind neurotransmitters directly to ion channels, opening them immediately.
• Metabotropic receptors involve a cascade of biochemical steps before opening ion channels.
• Neurotransmitters detach from receptors, channels return to resting states, and neurotransmitters are broken down or reabsorbed.

Neurotransmitters and Their Roles

• Excitatory and inhibitory actions determined by specific neurotransmitters.
• Excitatory neurons create neurotransmitters that depolarize membranes.
• Inhibitory neurons create neurotransmitters that hyperpolarize membranes.
• Glutamate is the brain's primary excitatory neurotransmitter, often binding to AMPA and NMDA receptors.
• GABA is the primary inhibitory neurotransmitter, and with ionotropic and metabotropic receptors, affects ion movement and membrane potential.

Receptors and Molecular Signaling

• Neurons have receptors for molecules like hormones, neuromodulators, and prostaglandins, which affect neuronal function differently.
• Hormones carry messages about distant body conditions and activities to the brain.
• Neuromodulators like endocannabinoids can affect release of other neurotransmitters.
• Prostaglandins can impact the brain's pain sensitivity.
• Intracellular changes occur following recognition of these chemical signals.
• Hormones (ex. steroid hormones) can enter neurons directly and affect gene expression.

Neurons, Genes, and Gene Expression

• Neurons differ in appearance and function, producing different neurotransmitters, and possessing unique receptor types.
• Identical genes, but cells express different subsets, creating neuronal diversity.
• Gene expression depends on chromatin state (tightly packed, accessible).
• Chemical changes in chromatin can either turn genes on or off, and these are reversible.
• Allele variations can affect protein function and cause neurological conditions (e.g., Tay-Sachs disease).
• Understanding of genetic basis of brain disorders is expected to grow with genome sequencing technology.