Neuroscience Basic Concepts

Grand questions in neuroscience

Understanding consciousness, mind-brain relations, and perception and behavior.

Reticular theory

The disproven idea that the nervous system is a continuous cell network.

Neuron doctrine

The principle that the nervous system consists of discrete, polarized cells called neurons.

Dendrites

Neuronal structures that receive inputs and contain microtubules.

Soma (Cell body)

Contains the nucleus and handles gene transcription and translation.

Axon

Sends output to other neurons and can exceed one meter in length.

Dendritic spines

Very small (< 1 µm) structures on dendrites that form synapses.

Synaptic vesicles

Vesicles in presynaptic boutons that contain neurotransmitters.

Ionotropic vs. metabotropic receptors

Ionotropic are channels; metabotropic trigger a signalling cascade.

Node of Ranvier

The electrical insulation gap between myelin sheaths on an axon.

Luigi Galvani

Discovered 'Animal Electricity' in 1771.

Ohm's Law

Expressed as V = IR, relating voltage, current, and resistance.

All-or-none action potentials

Action potentials are always the same height once threshold is reached.

Axonal cytoskeleton

Microtubules for transport and neurofilaments for structural stability.

Membrane potential equilibrium

Reached when the electrical driving force is equal and opposite to the chemical driving force.

Nernst equation

Used to calculate equilibrium potential for a single ion, expressed as Vm = 58 mV log([K]out/[K]in).

Signalling efficiency

Membrane potential changes efficiently because very few ions move (

Role of transporters

Establish ion gradients by working against concentration gradients, which requires energy from ATP.

Goldman-Hodgkin-Katz equation

An equation that calculates membrane potential by factoring in multiple ions and their relative permeabilities.

Nernst vs. GHK Prediction

GHK predicts membrane potential more accurately than the Nernst equation by factoring in multiple ions and relative permeabilities.

Resting Membrane Permeabilities

The resting membrane is permeable to K+, Cl-, and Na+, with PK > PCl > PNa.

Action Potential Phases

Includes depolarization to positive values, repolarization, and afterhyperpolarization going more negative than rest.

Voltage Clamp Technique

An experimental method where the experimenter sets command voltage and the amplifier measures injected current to keep voltage constant.

Voltage Clamp Conductance

Measures conductance changes since g = I / V, reflecting ion channels opening and closing.

Voltage Clamp Currents

Depolarizing an axon to 0 mV reveals an early inward Na+ current and a delayed outward K+ current.

TTX (Tetrodotoxin)

Binds to the Na+ channel pore at the selectivity filter to block early inward sodium currents.

TEA (Tetraethylammonium)

Blocks delayed rectifier potassium channels, eliminating the late outward current.

Hodgkin-Huxley gating mechanisms

Voltage-sensitive charged gates controlling channels; Na+ has 3 activation and 1 inactivation gate, while K+ has 4 activation gates.

Positive feedback in action potentials

Na+ channel activation causes membrane depolarization, driving the all-or-none property.

Action potential propagation

Current from open Na+ channels depolarizes nearby membrane patches, advancing the signal down the axon.

Absolute refractory period

Time when Na+ channels are inactivated and cannot be activated again until membrane repolarizes.

Length constant (l)

Rate of decay of depolarization with distance along an axon; larger l means current travels further.

Cable theory

Mathematical description of current spread along axons, pioneered by Lord Kelvin.

Myelination and conduction velocity

Myelin increases membrane resistance, increasing the length constant to speed up conduction.

Saltatory conduction

Rapid propagation of action potentials jumping from one node of Ranvier to the next.

Voltage-gated ion channel superfamily

A diverse group of 143 genes with varied ion selectivity and gating mechanisms.

Shaker mutation

A mutation in Drosophila K+ channels discovered when flies shook their legs under ether anesthesia.

Potassium channel structural subunits

Consist of six transmembrane domains (S1-S6), with S4 acting as the voltage sensor and a pore loop between S5 and S6.

KcsA channel

A bacterial potassium channel lacking S1-S4 voltage sensors, used in X-ray crystallography studies by MacKinnon.

KcsA selectivity filter

Contains inward-facing oxygen atoms spaced to fit dehydrated K+ while excluding Na+.

Types of potassium channel diversity

Includes leak channels, delayed rectifiers, Shaker channels, and calcium-activated potassium channels.

Sodium channel domains

Composed of four linked domains (I-IV) with an inactivation gate located in the loop between domains III and IV.

Calcium channel types

Includes N- and P-type for synaptic transmission, T-type for small depolarizations, and L-type for muscle contraction.

Neher and Sakmann technique

Developed the technique to record currents from individual channels in voltage clamp.

Microscopic Na channel currents

Opens transiently at random times for a short duration with only two conductance states: open or shut.

Neurotransmitter functional classes

Categorized as excitatory (acetylcholine, glutamate), inhibitory (GABA, glycine), or modulatory.

Acetylcholine receptor types

Includes ionotropic nicotinic receptors and metabotropic muscarinic receptors.

Acetylcholine pharmacology

Nicotine and muscarine act as agonists, while curare and atropine act as antagonists.

Nicotinic Acetylcholine Receptor (nAChR)

A pentameric, non-selective cation channel permeable to K+, Na+, and Ca2+ that produces an excitatory response.

Acetylcholinesterase (AChE)

An enzyme in the synaptic cleft that terminates transmission by cleaving ACh into choline and acetate.

Myasthenia gravis

An autoimmune condition where antibodies attack AChRs, leading to muscle weakness and droopy eyelids.

AMPA Receptors

Tetrameric glutamate receptors permeable to K+ and Na+ that drive fast postsynaptic electrical responses.

NMDA Receptors

A glutamate receptor featuring a voltage-dependent Mg2+ block, acting as a Ca2+ permeable coincidence detector for learning and memory.

Glutamate Recycling Mechanism

Glia clear glutamate, convert it to glutamine, and pass it to neurons where it is converted back into glutamate.

Ionotropic GABA and Glycine Receptors

Pentameric inhibitory receptors that conduct Cl- ions to reduce the likelihood of firing an action potential.

Alzheimer's Cholinergic and Glutamatergic Treatments

Aricept acts as an AChE antagonist to enhance ACh signaling, while Namenda is an NMDA antagonist preventing Ca2+ toxicity.