Neuroscience Fundamentals: Neurons and Glia

• Neuroscience explores the nervous system, serving as a foundational subject for pharmacy students to understand structure and function.
• Focus is given to the central (CNS) and peripheral (PNS) nervous systems, including brain, spinal cord, and peripheral nerves.

Brain Areas

• Regions of the brain orchestrate cognition, emotions, and physiological functions.
• Understanding is key to insights into neurological disorders and drug actions.
• The cerebral cortex is the brain's outermost layer, responsible for diverse functions, divided into four lobes.
• The frontal lobe, located at the front, controls executive functions like decision-making and emotional regulation.
• The prefrontal cortex is a subsection critical for high-order cognitive processes, influenced by development and environment.
• Temporal lobes, on the sides, manage auditory processing, language comprehension, and memory formation.
• The parietal lobe integrates sensory information, enabling spatial awareness and perception, contains somatosensory cortex manages tactile information such as touch and temperature.
• The occipital lobe, at the back, handles visual processing.
• The limbic system, including the amygdala, hippocampus, and hypothalamus, is involved in emotions, memory, and autonomic regulation.
• The hippocampus is the primary memory processing center, assisting short-term memories become long-term memories.
• The amygdala modulates emotional responses and formations of emotional memories.
• The basal ganglia, are deep within the brain, responsible for motor control, procedural learning, and habit formation.
• The brainstem, connecting to the spinal cord, regulates autonomic functions like breathing and heartbeat.
• The cerebellum, is located at the back of the brain, responsible for coordination, balance, and motor learning.
• The corpus callosum, a nerve fibre bundle, connects brain hemispheres, allowing for communication and integration.

Blood Brain Barrier

• The blood-brain barrier (BBB) is specialized for protecting the brain.
• The BBB uses endothelial cells and tight junctions to control substance passage between the bloodstream and brain tissue.
• Tight junctions prohibit molecule diffusion between cells.
• Permeability allows essential nutrients like oxygen and glucose to pass, while larger or harmful substances require transporters or are actively pumped out.
• Transporters facilitate nutrient entry and homeostasis.
• The BBB acts as a protective shield, regulator, and gatekeeper.
• P-glycoproteins act as efflux proteins to protect the CNS from toxic substances, accounting for the limited effects of certain drugs.
• BBB integrity is critical as disruptions can contribute to inflammation or neurodegeneration.

Peripheral Nervous System

• The peripheral nervous system (PNS) connects the brain and spinal cord to organs, muscles, and tissues.
• A network of nerves facilitates communication using both sensory and motor neurons.
• Sensory neurons relay signals to sensory receptors in the brain, enabling the perception of external stimuli.
• Motor neurons transport instructions, coordinating voluntary and involuntary actions.
• The PNS comprises the somatic nervous system, which governs voluntary movements, and the autonomic nervous system, which regulates involuntary functions.
• It further divides into the sympathetic and parasympathetic divisions to maintain homeostasis.

Types of Neurons

• Projection neurons, are known as principal or output neurons, transmit information over long distances.
• Interneurons are local circuit neurons modulating activity in specific brain regions.
• Glial cells are crucial for maintaining neuron health, synaptic activity, and brain homeostasis.
• Astrocytes contribute to neural function by supporting the extracellular environment and modulating neurotransmitter levels.
• Oligodendrocytes and Schwann cells insulate axons with myelin sheaths, enhancing electrical signal conduction.
• Microglia are immune cells that detect disturbances and resolve neural damage.
• Ependymal cells regulate cerebrospinal fluid (CSF) production and neural stem cells.
• Radial glial cells guide migrating neurons during development and contribute to neurogenesis.

Neuron Components

• Neurons consist of the soma or cell body, which directs operations, and dendrites, which receive signals.
• The axon transmits electrical impulses.
• A myelin sheath insulates, enabling rapid signal conduction, with nodes of Ranvier accelerating transmission.
• At the axon terminal, neurotransmitters are released to communicate with other neurons across the synapse.

Neurophysiology

• Neurons use electrical and chemical signals for communication.
• Neurons maintain a resting membrane potential, a charge differential across the plasma membrane.
• Concentrations of Na+ and Ca2+ are higher outside the cell, balanced by K+ gradient and intracellular proteins.
• The Na+/K+ pump maintains resting potential, requiring ATP, polarizing the neuronal cell.
• Neurons can reverse resting potential via ion channel activity, which are ligand gated and voltage gated.
• Ligand-gated channels open with extracellular agonist binding, allowing ion passage through the cell membrane.
• Glutamate activates NMDA and AMPA glutamatergic cation channels, making membrane potential less negative.
• Voltage-gated Na+ channels trigger action potentials in excitable cells when membrane potential changes.
• Na+ influx causes depolarization, ending when channels close and allowing repolarization.
• Inactivation gates ensure unidirectional flow through channels, preventing immediate reactivation.
• The influx of sodium ions generates an action potential and rapid voltage change along the axon.
• Neuronal sodium channels open with membrane depolarization, leading to all-or-none action potential.
• The effect of depolarization increases K+ flow; voltage-gated K+ channels open, and K+ rushes out, helping repolarize the membrane.

Saltatory Conduction

• In myelinated axons, signal transmission appears to jump between Nodes of Ranvier.
• This process uses fast, degrading graded potentials under myelin and action potentials at the Nodes.
• The signal degrades but remains above the threshold at the next node, enabling an action potential to occur.
• Depolarization occurs through voltage-gated Ca2+ channels at the axon terminal to trigger neurotransmitter release into the synaptic space.
• A reuptake mechanism recycles neurotransmitters back into the presynaptic neuron to prevent overstimulation.

Postsynaptic Potentials and Synapses

• Inhibitory interneurons which utilize GABA, function to suppress the activity of adjacent cells.
• GABA affects activity through GABAa and GABAb receptors.
• GABAa receptors are chloride channels causes a hyperpolarization of the membrane.

Signalling

• Hyperpolarization occurs with GABA receptors which use G protein signaling to activate cellular changes and are slower and longer lasting.
• Inhibitory or excitatory interneurons release neurotransmitters to slightly depolarize or hyperpolarize the membrane.
• Neuromodulators control network firing frequency and amplitude, signaling via G protein-coupled receptors.
• Excitatory neurotransmitters promote activity by depolarizing the membrane, increases permeability to Na+ ions or decreases permeability to K+ ions.
• Inhibitory neurotransmitters decrease activity by hyperpolarizing the membrane, increases permeability to Cl or K+ ions.

Glutamate

• Glutamate is critical for neural communication and promotes synaptic plasticity.
• It stimulates postsynaptic neurons and helps with influencing functions like learning and memory.
• Glutamate can lead to excitotoxicity if it is released in excess.

Acetylcholine

• Acetylcholine aids muscle control, memory, and attention by acting on muscarinic and nicotinic CNS and PNS receptors.
• ACh is essential for signals which go to the muscles.
• Imbalances lead to cognitive deficits.

GABA

• GABA regulates excitability by binding to GABA receptors, prevents overstimulation and regulates anxiety which prevents overstimulation.
• Dysfunction leads to neurological and psychiatric disorders.

Neuromodulators

• Neuromodulators alter neuronal activity and circuit function over time.
• Types of neuromodulators include are like serotonin, dopamine, and norepinephrine.
• They affect the activity of other neurons, synaptic strength, neuronal excitability, regulating neurotransmitter release, modulating neural plasticity.
• They play a essential role in how the brain functions such as mood, motivation, attention, learning, memory, and pain perception which creates target for pharmacological interventions.

Monoamines

• Monoamine neuromodulators adjust activity and regulate processes in the brain.
• They contain a single amine group which include Serotonin, dopamine, and norepinephrine.
• Their effects are prolonged effects on neural circuits
• Help to regulate mood, arousal, and attention.

Serotonin

• Serotonin regulates sleep, mood, appetite, and well-being by interacts with serotonin receptors.
• Imbalances are related to mood disorders, may be treated with SSRIs.

Dopamine

• Dopamine influences cognition and motor function by acting on dopamine receptors.
• Roles include actions relating to reward, behavior, motivation, and motor control.
• Dysregulation is implicated in addiction, Parkinson's disease, and schizophrenia.

Norepinephrine

• Norepinephrine modulates stress, arousal, and attention by acting on adrenergic receptors.
• It contributes to fight-or-flight.
• Links relate to ADHD and PTSD.

Neurotransmitter Receptors

• Neurotransmitter receptors are specialized proteins on the surface of neurons, which affects communication between neurons.
• Ionotropic receptors are linked to ion channels and cause fast membrane potential changes which create a fast, short action.
• Metabotropic receptors signal via G proteins, modulate slower changes.

Neural Networks

• Neural networks form from interconnected neurons and the transmission of information in the form of electrical impulses.
• During embryonic development networks are formed via a process called neurogenesis.
• Once in their designated spots, neurons produce axons and dendrites to connect to others and do not undergo mitosis in adults.

Synaptic Formation

• Synapses and synaptic connections happen through synaptogenesis.
• Initially sparse, synaptic connections happen.
• Sprouting is the growth of new synapses, and pruning removes extra synapses.

Synaptic Plasticity:

• Synapses can either strengthen or weaken over time, which is is known as synaptic plasticity.
• This ability is important for learning and memory formation.
• Synapses include Long-Term Potentiation (LTP), synapses strengthen, and Long-Term Depression (LTD), where synaptic connections weaken.

Temporal and Spatial Summation

• Temporal and spatial summation mechanisms occur when neurons integrate incoming signals determine whether to generate an action potential.
• Temporal summation occurs when multiple signals from one neuron arrive at the postsynaptic neuron.
• Spatial summation is signals that are simultaneous from multiple presynaptic arrive at the postsynaptic neuron.
• If the combined effects of the signals, in either case reach the threshold, an action potential occurs.

Test your knowledge of neuroscience fundamentals, including neuron function, glial cells and the blood-brain barrier. Questions cover membrane potential, depolarization, and the roles of different cell types.