Neurobiology: Membrane Potential and Neuronal Activity and the Biophysics of Behavior

Neural Coding of Complex Behavior

• Recognition as a Kinetic Process: Instead of having a single dedicated neuron for a specific complex recognition—such as the hypothetical "Professor Knowles neuron"—recognition is a kinetic process involving networks of neurons.
• Overlapping Neural Sets: Recognition of a specific face or person relies on overlapping sets of neurons that have been utilized throughout a person's life to recognize other faces.
• Coding for Properties: High-level recognition is built on coding for specific properties, such as the structure of glasses, physical positioning (e.g., being on a stage), and verbal attributes.
• Elastic Cell Neurons: There are individual neurons (sometimes called "elastic cell neurons") that respond to very specific stimuli. Evidence for this comes from neurosurgical recordings where patients are kept conscious during brain surgery.
  • Neurosurgical Insights: Because the brain itself lacks pain receptors (headache pain originates from outside the brain), doctors can record from or stimulate specific neurons while the patient is awake.
  • Stimulation Effects: Stimulating a single neuron embedded in a complex network can elicit a persistent and consistent thought or image of a specific celebrity or work.

Muscular Dynamics and Baseline Neuronal Activity

• Skeletal Muscle State: Skeletal muscles are rarely at a state of total relaxation. Most muscles maintain a degree of contraction or tone at all times.
• Mechanisms of Variation in Contraction: Variation in muscular contraction can occur through several pathways:
  • Episodic Neurotransmitter Release: This occurs at the neuromuscular junction.
  • Sliding Filament Mechanism: Physical contraction occurs as myosin slides across actin filaments.
  • Calcium Variance: Fluctuations in calcium levels can cause switching in the contraction mechanism independent of direct neural activity.
• Baseline Activity: Behavior must be viewed against a baseline of activity. This "current state" is constantly shifting because the organism is never in a perfectly static state, nor would it be advantageous to be.

Biophysical Properties of the Neuron

• Structural Components:
  • Dendrites: Represented by horizontal lines in diagrams, these are the primary input zones collecting information from thousands of other neurons.
  • Cell Body (Soma): Integrates incoming signals.
  • Axon and Terminals: The flow of information from the axon hillock to the terminals is purely electrical.
• The Neuron as a Capacitor: The neuronal membrane acts as a capacitor, storing electrical charge.
  • Insulation: The membrane structure itself is non-conducive and acts as an insulator.
  • Aqueous Solutions: The solutions inside and outside the cell allow for the free movement of ions.
• Gradients Driving Ion Movement:
  • Concentration Gradient: Ions move from areas of high concentration to low concentration.
  • Voltage Gradient: Charged particles move based on electrical attraction and repulsion (opposite charges attract).
• Resting Membrane Potential: The homeostasis or "steady state" of a neuron in the theoretical absence of stimulation.
  • Charge Distribution: The inside of the neuron is negative relative to the outside.
  • Quantitative Value: A normal resting potential is approximately $-70\,mV$.
  • Battery Analogy: The stored charge in a neuron functions like the potential energy in a battery, which can be tapped to perform work (neural signaling).

The Mechanism of the Resting Membrane Potential

• Ion Distributions:
  • Potassium ($K^+$): Concentration is significantly higher inside the neuron than outside.
  • Sodium ($Na^+$): Concentration is higher outside the neuron than inside.
  • Anions ($A^-$): Represent internal proteins that carry a net negative charge. While mentioned in texts, they do not contribute meaningfully to the actual potential change across the membrane.
• Non-Gated Ion Channels: These channels flip between open and closed states without a specific gating trigger.
  • Selectivity Filter: Channels have pores specific to certain ions (e.g., Potassium channels).
  • Hydration Cloud: In aqueous solution, ions attract water molecules. To pass through a channel, the "water molecules of hydration" must be stripped from the ion.
• Differential Permeability: There are significantly more potassium channels than sodium channels.
  • Ratio: There are approximately $20$ to $25$ times more potassium channels than sodium channels.
• The Net Flux Equilibrium:
  • Potassium leaves the cell down its concentration gradient, making the inside more negative.
  • As the inside becomes negative, the voltage gradient begins to pull potassium back in and pull sodium in more strongly.
  • The system reaches a steady state at $-70\,mV$, where the net efflux of potassium equals the net influx of sodium.

The Sodium-Potassium Pump and Metabolic Regulation

• Function: To maintain the concentration gradients. Without the pump, concentrations would equalize, the voltage would dissipate, and the "battery" would die.
• Rate-Limiting Steps of the Sodium-Potassium Pump ($Na^+/K^+$ ATPase):
  1. Sodium Binding: There are three binding sites for sodium on the intracellular side. The pump's activity increases as internal sodium concentration increases.
  2. ATP Availability: The pump is an ATPase. It hydrolyzes ATP to change its configuration, moving sodium out and potassium in.
• Feedback Mechanism and Blood Flow:
  • Astrocyte Role: These glial cells pick up excess potassium expelled by neurons.
  • Nitric Oxide ($NO$): The intake of potassium by astrocytes triggers the release of nitric oxide gas.
  • Vasodilation: Nitric oxide causes epithelial cells to dilate, increasing blood flow to active areas.
  • Brain Mapping: Technologies like fMRI or PET scans often measure these changes in blood flow as a proxy for neural activity.

Physiological Significance and Survival Advantages of the Resting Potential

• Excitability and Thresholds: Setting the resting potential at $-70\,mV$ determines how much stimulus is needed to reach the firing threshold.
  • Threshold Value: For most neurons, the threshold for an action potential is between $-55\,mV$ and $-50\,mV$.
  • Sensitivity: A resting potential closer to the threshold (e.g., $-70\,mV$ vs $-90\,mV$) makes a neuron more excitable and requires less summation of input to fire.
• Directionality (Hyperpolarization vs. Depolarization): Keeping the potential away from the equilibrium potential for potassium allows the neuron to move in two directions:
  • Depolarization: Becoming more positive (moving toward the threshold).
  • Hyperpolarization: Becoming more negative (moving further from the threshold, acting as an inhibitory signal).
• State Switching: Variations in resting potential allow organisms to shift between physiological states, such as sleep-wake cycles.
  • Sleep: Neuropeptides can shift resting potentials to a more negative state, making neurons less sensitive to stimuli and maintaining the sleep state.
  • Modulators: Hormones, neuropeptides (like endorphins), and neurotransmitters can adjust these potentials.

Neural Signaling and Synaptic Integration

• Summation: Signals are integrated both spatially (across different locations on the dendrites) and temporally (over time).
• Neurotransmitter-Gated Ion Channels: These channels respond to chemical signals.
  • Binding Requirements: Most of these channels have two binding sites for neurotransmitters; both must be occupied to shift the channel into the open state.
  • Mechanism: When the neurotransmitter binds, the channel shifts from a stable closed configuration to an open one, allowing ions to move and changing the membrane potential.

Questions & Discussion

• Question on Muscle and Glial Potentials: A student asked about the energy cost of resting potentials in other cells.
  • Response: Professor Knowles confirmed that muscles and glia also have resting potentials (often driven primarily by potassium). He noted that while energy use is a metabolic cost, natural selection favors this "readiness" state because it allows for greater adaptability and survival competition.
• Question on Cognition and Inherent Potentials: A student asked if animals with lower cognitive potential have different resting potentials.
  • Response: Resting potentials are remarkably consistent across species. A nematode worm has resting potentials similar to a human. The difference in behavior is due to network complexity, not the fundamental biophysics of the individual neurons.
• Question on Epilepsy and Seizures: A student inquired if seizures are caused by a lower (more positive) resting potential.
  • Response: This is a viable hypothesis, as a resting potential closer to the threshold would increase the likelihood of firing. Current research often focuses on chloride channels as a potential cause of epilepsy. Chloride usually acts as an inhibitory input, but if its movement direction changes, it can become excitatory.