What is the electrophysiology of neurons?

Electrophysiology of Neurons: A Comprehensive Overview

Neuronal electrophysiology fundamentally depends on transmembrane currents that generate electrical signals through active and passive mechanisms, with these signals propagating through brain tissue according to volume-conductor theory and cable theory principles. 1

Fundamental Biophysical Principles

Transmembrane Current Generation

Transmembrane currents passing through neuronal and glial cell membranes form the basis of all electrical brain signals. 1 These currents arise from:

• Active mechanisms: Ion channel-mediated currents driven by electrochemical gradients 1
• Passive mechanisms: Capacitive coupling between conductive elements across the membrane 1
• Balanced current flow: Cable theory dictates that the sum of transmembrane ionic and capacitive currents across the entire cellular surface must equal zero, meaning currents entering the cell at one location must be balanced by currents leaving at other locations 1

Volume-Conductor Theory

Volume-conductor theory explains how electrical signals propagate from their cellular sources through brain tissue to recording electrodes. 1 This theoretical framework:

• Provides the biophysical basis for all extracellular signal recordings 1
• Allows generation of extracellular signals from transmembrane currents using biophysically detailed multicompartment neuron models 1
• Accounts for signal propagation through the conductive medium of brain tissue 1

Neural Oscillations and Rhythmic Activity

Oscillatory Fundamentals

Neural oscillations reflect cyclic waxing and waning of excitation in brain regions, making these regions temporarily more susceptible to inputs during specific excitable phases of the oscillatory cycle. 1 These rhythms constitute the fundamental building blocks of cognition:

• Temporal structure: Rhythmic brain activity supports representation, processing, and prediction of sensory information across multiple time scales 1
• Functional basis: This temporal organization forms the basis of both action and cognition 1

Frequency-Specific Functions

Different oscillatory frequencies subserve distinct cognitive and perceptual functions. 1

• Gamma oscillations (40-100 Hz): Linked to low-level sensory processing and perceptual binding 1
• Alpha and theta bands: Associated with higher-order perception, attentional control, and memory functions 1

Neuronal Electrogenesis and Recording Techniques

Electroencephalography (EEG)

The EEG primarily reflects cortical neuronal activity modulated by physiological and pathological diencephalic and brainstem influences, as well as metabolic and toxic factors. 1 Key characteristics include:

• Cortical focus: EEG patterns predominantly capture cortical function 1
• Sensitivity: Neuronal electrogenesis depends on energy-providing metabolic systems, electrolyte homeostasis, and toxic substance clearance 1
• Clinical utility: Provides quantitative assessment amenable to follow-up, remaining interpretable even in patients under muscle blockade where clinical examination is not feasible 1

Evoked Potentials (EPs)

Evoked potentials are generated through passive reception of sensory stimuli (exogenous EPs) or cognitive treatment of sensory stimuli (endogenous/cognitive EPs). 1

Classification systems:

• By stimulus type: Visual (VEP), auditory (AEP), or somatosensory (SEP) 1
• By latency: Short-latency, middle-latency, or long-latency EPs 1
• Cortical sensitivity: Cognitive EPs (P300 paradigm), visual EPs (latency >100 ms), and somatosensory EPs (latency 25-100 ms) reliably reflect cortical function 1

Cellular Electrophysiology and Field Potentials

Spatial Summation and Dipole Formation

Field potentials sum activity from all electrically active membranes and transmembrane current generators in space and time, from axon terminals to soma, encompassing action potentials to very slow conductances. 1

Geometric factors dominate field potential generation more than source strength. 1

• Open field configuration: Spatially separated positive and negative sources create relatively large mesosources even with small underlying microsource magnitudes 1
• Closed field configuration: Symmetrically distributed microsources produce small resulting mesosources because dipoles cancel each other, even when individual microsources are large 1
• Pyramidal neuron advantage: These neurons, the most numerous in hippocampus and cortex, have extended dendritic arbors creating open fields 1

Synaptic Contribution

Measurement projections from field potential recordings preferentially weight postsynaptic potentials in neurons with open-field geometry and spatially organized synaptic inputs. 1

• Optimal configuration: Synaptic inputs onto either basal or apical dendrites that are temporally correlated generate the largest extracellular potentials 1
• Cancellation effects: Evenly distributed synaptic inputs cause transmembrane currents to cancel, generating small extracellular potentials 1

Neuronal Firing Properties and Action Potentials

Dopaminergic Neuron Electrophysiology (Example Model)

Spontaneously firing neurons exhibit characteristic electrophysiological signatures including slow depolarizing potentials driving spike activity and specific spike thresholds. 2

Spike activity depends on four depolarizing events:

• Voltage-dependent slow depolarization: TTX-sensitive mechanism 2
• Low threshold depolarization: Cobalt-sensitive, activated during rebound from brief membrane hyperpolarizations 2
• High threshold dendritic calcium spikes: Give rise to spike afterhyperpolarization 2
• High threshold initial segment sodium spike: Standard action potential mechanism 2

Modulating Processes

Multiple processes modulate neuronal depolarizations. 2

• Delayed repolarization: 4-aminopyridine-insensitive mechanism 2
• Anomalous rectification: Both instantaneous and time-dependent components 2
• Afterhyperpolarization: Follows action potential generation 2

Clinical and Research Applications

Functional Assessment Capabilities

Neurophysiological investigations provide functional assessment of the nervous system through studying neuronal electrogenesis, offering quantitative measures for follow-up that complement clinical examination. 1

Temporal and Spatial Resolution

Electrophysiology provides real-time readout of neural functions and network capability on temporal scales (fractions of milliseconds) and spatial scales (micro, meso, and macro) unmet by other methodologies. 3

This allows examination of:

• Neural excitation/inhibition balance: Direct measurement of neurotransmission 3
• Brain network dynamics: Assessment of synchronization and functional connectivity 3
• Thalamocortical and corticocortical capacity: Evaluation of residual brain network function 3

Ion Channel Physiology

Ion channels serve as critical therapeutic drug targets due to their involvement in neuronal signaling and cardiac excitability. 4 Patch clamp techniques (conventional and automated) represent the gold standard for studying:

• Physiological properties: Normal channel function 4
• Pharmacological properties: Drug effects on channels 4
• Biophysical properties: Detailed channel kinetics and conductance 4