🧢Neuroscience Unit 2 – Neurophysiology and Signaling

Key Concepts and Terminology

• Neuron the fundamental unit of the nervous system, responsible for receiving, processing, and transmitting information
• Synapse the junction between two neurons where information is passed from one neuron to another
• Neurotransmitter chemical messenger released by neurons at synapses to transmit signals to other neurons or target cells
• Ion channel protein complex that forms a pore in the cell membrane, allowing specific ions to pass through
• Membrane potential the difference in electrical charge between the inside and outside of a neuron's cell membrane
• Action potential a brief, rapid change in the membrane potential that propagates along the axon of a neuron
• Resting potential the stable, negative membrane potential of a neuron when it is not actively transmitting a signal (typically around -70 mV)
• Threshold the membrane potential at which an action potential is triggered (typically around -55 mV)

Neuronal Structure and Function

• Neurons are highly specialized cells consisting of a cell body (soma), dendrites, and an axon
  • Soma contains the nucleus and other organelles necessary for cellular function
  • Dendrites are branched extensions that receive signals from other neurons
  • Axon is a long, thin extension that conducts electrical signals away from the soma
• Neurons are classified into three main types based on their function
  • Sensory neurons detect and transmit information from sensory receptors to the central nervous system
  • Motor neurons transmit signals from the central nervous system to muscles or glands
  • Interneurons connect sensory and motor neurons within the central nervous system, processing and integrating information
• Glial cells are non-neuronal cells that support and maintain the nervous system
  • Astrocytes provide structural support, regulate neurotransmitter levels, and maintain the blood-brain barrier
  • Oligodendrocytes and Schwann cells form myelin sheaths around axons, insulating them and increasing the speed of signal transmission
  • Microglia are the immune cells of the nervous system, responding to injury and infection
• Neurons communicate with each other and target cells through a combination of electrical and chemical signaling

Membrane Potential and Ion Channels

• The membrane potential is determined by the unequal distribution of ions (primarily sodium, potassium, and chloride) across the cell membrane
• Ion channels are selectively permeable to specific ions and can be gated by various stimuli (voltage, ligands, or mechanical forces)
• The resting potential is maintained by the sodium-potassium pump (Na⁺/K⁺-ATPase), which actively transports sodium ions out of the cell and potassium ions into the cell
  • This creates a concentration gradient, with higher concentrations of sodium outside the cell and potassium inside the cell
• The resting potential is also influenced by the permeability of the cell membrane to different ions
  • At rest, the membrane is more permeable to potassium than sodium, allowing potassium to leak out of the cell along its concentration gradient
• The Goldman-Hodgkin-Katz equation describes the relationship between ion concentrations, permeabilities, and the membrane potential
  • $V_m = \frac{RT}{F} \ln \frac{P_{K^+}[K^+]_o + P_{Na^+}[Na^+]_o + P_{Cl^-}[Cl^-]_i}{P_{K^+}[K^+]_i + P_{Na^+}[Na^+]_i + P_{Cl^-}[Cl^-]_o}$
• Changes in the membrane potential can lead to the opening or closing of voltage-gated ion channels, which are crucial for the generation and propagation of action potentials

Action Potentials and Propagation

• Action potentials are brief, all-or-none electrical events that allow neurons to transmit signals over long distances
• The generation of an action potential involves the opening and closing of voltage-gated sodium and potassium channels
  • Depolarization occurs when the membrane potential becomes less negative, typically due to the opening of sodium channels and the influx of sodium ions
  • If the membrane potential reaches the threshold (around -55 mV), an action potential is triggered
• The rising phase of the action potential is caused by the rapid opening of voltage-gated sodium channels, leading to a massive influx of sodium ions
• The falling phase is caused by the inactivation of sodium channels and the delayed opening of voltage-gated potassium channels, leading to an efflux of potassium ions
• After the action potential, the membrane potential undergoes a brief hyperpolarization (afterhyperpolarization) before returning to the resting state
• Action potentials propagate along the axon through a process called saltatory conduction
  • The myelin sheath insulates the axon, allowing the action potential to jump from one node of Ranvier to the next
  • This increases the speed of signal transmission and conserves energy

Synaptic Transmission

• Synaptic transmission is the process by which neurons communicate with each other or target cells at synapses
• Electrical synapses are gap junctions that allow direct, bidirectional flow of ions and small molecules between connected cells
  • They are fast and do not involve neurotransmitters
• Chemical synapses are more common and involve the release of neurotransmitters from the presynaptic neuron, which bind to receptors on the postsynaptic cell
  • The arrival of an action potential at the presynaptic terminal triggers the opening of voltage-gated calcium channels
  • The influx of calcium ions causes synaptic vesicles containing neurotransmitters to fuse with the presynaptic membrane and release their contents into the synaptic cleft
• Neurotransmitters diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell
  • This can lead to the opening or closing of ion channels, resulting in either excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs)
• The strength of synaptic transmission can be modulated by various factors, such as the amount of neurotransmitter released, the number and sensitivity of postsynaptic receptors, and the activity of neurotransmitter transporters

Neurotransmitters and Receptors

• Neurotransmitters are chemical messengers that transmit signals across synapses
• The main classes of neurotransmitters include amino acids (glutamate, GABA, glycine), monoamines (dopamine, serotonin, norepinephrine), acetylcholine, and neuropeptides (endorphins, substance P)
• Neurotransmitter receptors are proteins that bind specific neurotransmitters and mediate their effects on the postsynaptic cell
• Ionotropic receptors are ligand-gated ion channels that open or close in response to neurotransmitter binding
  • Examples include AMPA and NMDA receptors for glutamate, and GABAA receptors for GABA
• Metabotropic receptors are G protein-coupled receptors that initiate intracellular signaling cascades upon neurotransmitter binding
  • Examples include mGluR receptors for glutamate, and GABAB receptors for GABA
• The effects of neurotransmitters are terminated by reuptake into the presynaptic neuron or glial cells, enzymatic degradation, or diffusion away from the synapse
• Neurotransmitter imbalances or receptor dysfunction can contribute to various neurological and psychiatric disorders

Neuronal Networks and Circuits

• Neurons are organized into complex networks and circuits that process and integrate information
• Feedforward circuits transmit information in a unidirectional manner, from input to output
  • Example the visual pathway, which transmits information from the retina to the primary visual cortex
• Feedback circuits involve recurrent connections that allow the output of a system to influence its input
  • Example the basal ganglia-thalamocortical loop, which is involved in motor control and learning
• Lateral inhibition is a common circuit motif in which the activation of one neuron inhibits the activity of neighboring neurons
  • This enhances contrast and sharpens the representation of sensory information
• Oscillations and synchronization of neuronal activity are important for various cognitive processes, such as attention, memory, and perception
  • Example gamma oscillations (30-80 Hz) are associated with conscious perception and working memory
• Plasticity is the ability of neuronal networks to change and adapt in response to experience or injury
  • Synaptic plasticity involves changes in the strength of synaptic connections, such as long-term potentiation (LTP) and long-term depression (LTD)
  • Structural plasticity involves changes in the number and arrangement of synapses and neurons

Clinical Applications and Disorders

• Understanding the principles of neurophysiology and signaling is crucial for diagnosing and treating neurological and psychiatric disorders
• Epilepsy is a disorder characterized by recurrent, unprovoked seizures resulting from abnormal, excessive, or synchronous neuronal activity
  • Anti-epileptic drugs target various ion channels and neurotransmitter systems to reduce neuronal excitability
• Parkinson's disease is a neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra
  • Treatments include dopamine replacement therapy (levodopa) and deep brain stimulation of the subthalamic nucleus or globus pallidus
• Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to synaptic dysfunction and neuronal loss
  • Current treatments are symptomatic and focus on enhancing cholinergic transmission (acetylcholinesterase inhibitors) and reducing glutamatergic excitotoxicity (memantine)
• Depression is a psychiatric disorder associated with imbalances in monoaminergic neurotransmission (serotonin, norepinephrine, and dopamine)
  • Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), increase the availability of these neurotransmitters in the synaptic cleft
• Schizophrenia is a psychiatric disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (apathy, social withdrawal), and cognitive deficits
  • Antipsychotic medications primarily target dopamine D2 receptors to reduce positive symptoms, but their efficacy for negative and cognitive symptoms is limited
• Advances in neuroimaging techniques, such as functional MRI and EEG, have enabled the study of brain activity and connectivity in health and disease, providing insights into the neural basis of behavior and cognition