Lecture 1 Notes
Organizational principles of the mammalian CNS
Dealing with complexity
Human brain: Contains approximately 10 - 10 neurons. Each communicates with 1000-10000 others
How to study the human brain: 1) defining the levels of organization. 2) identifying mechanisms and
structures within these levels so that generalizations can be made
Systems level of brain organization
Serial organization: Information that flows sequentially through different brain structures. For example:
Sensory receptors Thalamus Primary sensory cortex Polymodal association cortex Prefrontal
cortex Premotor cortex Motor cortex Spinal motor neurons
Parallel organization : information that is broken down / segregated into 'channels' and transmits
information in parallel with other distinct aspects of information.
Hierarchical organization and independence
Hierarchy: Cortical regions assert a top down control over 'subcortical' structures. Lower centers of the
brain is still capable of functioning independently
Striatalnigralstriatal dopamine pathway: Projections from the shell of the striatum (a major
component of the basal ganglia) innervate areas of the ventral tegmental area which in turn projects
to the striatal region adjacent to the shell, the core region The core in turn projects to areas of the
substantia nigra which then sends a dopamine projection to the more dorsal parts of the striatum. In
this way, ventral striatal regions influence more dorsal striatal regions via spiraling SNS projections.
Topography: Sensory receptors located close together project to neurons in the thalamus and cortex
that are physically close together. This is reflected in the sensory and motor homunculi reflected in the
sensory and motor cortices, as well as the retinotopic and tonotopic maps of their respective cortices.
Neuron - basic structural and functional unit of the CNS
Information flow: Generation of action potentials across chains of connected neurons
Dendrites: Region where one neuron receives connections from other neurons. Dendrites receive
synapses of many types and from many different presynaptic neurons.
Cell body / Soma: Contains the nucleus and the other organelles necessary for cellular function Axon: a key component of nerve cells over which information is transmitted from one part of the
neuron (usually the cell body) to the terminal regions of the neuron (terminal boutons) . Axons can be
rather long, extending up to a meter in sensorimotor nerve cells
Terminal bouton / Synapse : The terminal region of the axon where a neuron forms a connection with
another and conveys information through the process of synaptic transmission
Synaptic transmission: The process through which information is propagated via a presynaptic neuron,
the synapse, and a postsynaptic neuron.
Types of neurons
Projection neurons: Have long axons and project to other areas of the brain (or body). Projection
neurons are usually excitatory.
Interneurons: Have shorter axons (or no axons) and remain within a specific brain region. Interneurons
are usually inhibitory
Electrical activity in neurons
The membrane potential
Electrical potential (Voltage): Generated by a separation of ionic charges across an impermeable
phospholipid cell membrane due to a charge gradient across the plasma membrane. The passage of ions
across the membrane is permitted only by virtue of ion channels (passive and active)
Passive ion channels: Allows for ions to move across the membrane passively (without the expense of
energy) due to concentration / electrical gradient
Active ion channels: Ions are actively pumped in and out against the concentration / electrical gradient
via the expense of ATP (energy)
Fick's law of diffusion: 1) Ions will flow down a concentration gradient (high to low) until a point of
equilibrium is reached. 2) As ions move down a concentration gradient, the movement of charged ions
creates a charge gradient such that the ions will then begin to move in the opposite direction.
Equilibrium potential: The point at which electrical and chemical forces are equal and opposite. Also
known as the reversal potential for an ion. At this point, there will be no net flow of ions
Nernst equation: By knowing the 1) temperature, 2) concentrations of the ion inside and outside, 3)
valence of the ion, we can work out the equilibrium of each ion (given the gas constant = 8.315 /
faraday's constant = 96.485). E ion= RT/zF x ln([ion]o/[ion]i
Application of Nernst equation: A miniscule change in the outside concentration of K+ causes a huge
change in the V :mIncreasing the [K+] outsidey 1 mM further depolarizes the E frKm -103 mV to -88.6 mV.
Consequently, increasing the [K+] inside 1 mM yields a non-negligible change in V m GHK equation: Deviations in the Nernst equation attributed to the fact that the cell membrane is
permeable to more than one type of ion prompted the need for a more accurate equation derivation.
The GHK equation is the weighted average of Nernst potentials for multiple ions, using relative
permeability as a weighing factor. V = RTmF x ln (p [K] +Kp [oa] +Na [Clo / pClK]+ip [Ka]+ip [Na] i Cl o)
Application of GHK equation: GHK underlines the importance of relative permeability of the cellular
membrane to different ion species in determining the membrane potential. Thus, if the cellular
membrane is equally permeable to K+ and Na+ ions, then the V would mosm likely be somewhere
between the equilibrium potentials for K+ and Na+
Resting membrane potential
Resting membrane potential: At rest, the cellular membrane is dominated by its permeability to K+.
However, the membrane potential is NOT equal to the equilibrium potential of K+. This is because the
membrane is also permeable to Na+ and Cl- (as calculated by the GHK equation). The resting potential is
also maintained by the activity of Na+/K+ ATPase pumps which actively pump out 3 Na+ out and 2 K+ in
for each ATP molecule.
K+/Na+ levels: K+ levels are kept high internally and low externally. [ACTIVE] / Na+ levels are kept high
externally and low internally [ACTIVE]. There also appears to be a constant background 'leak' of K+ ions
through K+ leak channels that pass larger outward than inward currents under physiological conditions
Action potential: In neurons, electrochemical and physical stimuli can evoke large transient changes in
the membrane potential called action potentials or nerve impulses. These impulses act as signals of
information in the CNS. The impulses are caused by the movement of ions (mainly Na+/K+) across the
membrane to redistribute charge. It is important to note that an action potential generation is primarily
driven by electrical changes rather than concentration changes.
Peak of action potential: Characterized by Na+ ion permeability (i.e. conductance, g increaseNa. Na+
ions flow INTO the neuron, bringing the membrane potential (V ) closer mo the equilibrium potential of
Na+ ions. Due to the influx of Na+ ions, the inside of the cell becomes more positive than the outside
Falling phase of action potential: The membrane becomes permeable to K+ ions and K+ ions flow OUT
of the neuron, bringing about repolarization (i.e., restoring the negative charge on the inside). This
phase is also known as the ABSOLUTE refractory period.
Absolute refractory period: When another action potential cannot be generated in the same neuron,
however strong the stimulus. APs cannot travel past one another, since they cannot pass through the
other's absolute refractory period. Hyperpolarization / Undershoot: Repolarization typically undershoots the resting potential to around -
90 mV, causing the cell to become hyperpolarized as increase in K+ permeability is relatively long lasting
and equilibrium potential of K+ is usually lower than the resting membrane potential. This is also known
as the RELATIVE refractory period.
Relative refractory period: Only a strong, above-threshold stimulus will trigger an action potential.
Ion channel activity during an action potential
Analysis of ion channel activity: The shape and time course of an AP is determined by the activation and
inactivation properties of voltage gated Na+/K+ channels. Both channels open in response to
depolarization but have different activation properties. Opening of voltage gated K+ channels are
generally slower (characteristic of the falling phase)
Importance of Na+ current in AP
Na+ channel activation: [STUDY] Reduction in extracellular Na+ concentration reduces the amplitude of
the AP. Support to the notion that at the peak of action potential, the membrane becomes highly
permeable to sodium. In contrast, Na+ channel inactivation is the basis of the refractory period.
Importance of K+ current in AP
K+ channel activation: The diversity of K+ channels give rise to diversity in the types of K currents
observed in the brain. They are responsible not only for the repolarization of the action potential, bu