Neurons - Study Notes

Neurons: The Building Blocks of the Nervous System

This module provides an overview of neurons, their structure, and communication methods within the nervous system. Neurons receive sensory information and plan/execute behavioral responses. Understanding neurons is crucial for advancing in psychology.

Learning Objectives

• Differentiate the roles of neurons and glia cells.

• Describe diffusion and electrostatic pressure in electrochemical communication.

• Define resting membrane potential, EPSPs, IPSPs, and action potentials.

• Explain axonal and synaptic communication.

Introduction

Understanding individual neuron function is essential to understanding how groups of cells function in the brain. Neurons have a structure that underlies their function.

Santiago Ramón y Cajal (1911) established that individual neurons are the structural and functional units of the nervous system. He based this on drawings of Golgi-stained tissue (named after Camillo Golgi).

Different stains visualize cells uniquely. Nissl stain labels the cell body, while Golgi stain fills the cell body and all its processes. Golgi stain stains only 1–2% of neurons, which allows you to distinguish individual cells.

Cajal's work suggested neurons were distinguishable processing units, opposing Joseph von Gerlach's theory of a continuous nerve network. Cajal and Golgi shared the Nobel Prize in Medicine in 1906 despite their disagreement.

Key Concepts

Neuron Anatomy

Basic terminology will be introduced before diving into electrochemical signals. It will cover: resting membrane potential, electrical conductance within a single neuron, and electrical conductance resulting in communication between neurons through a release of chemicals.

Terminology Note

This module introduces a vast amount of technical terminology that at times may feel overwhelming. Do not get discouraged or bogged down in the details. Utilize the glossary at the end of the module as a quick reference guide; tab the glossary page so that you can easily refer to it while reading the module. The glossary contains all terms in bold typing. Terms in italics are additional significant terms that may appear in other modules but are not contained within the glossary. On your first read of this module, I suggest focusing on the broader concepts and functional aspects of the terms instead of trying to commit all the terminology to memory. That is right, I said read first! I highly suggest reading this module at least twice, once prior to and again following the course lecture on this material. Repetition is the best way to gain clarity and commit to memory the challenging concepts and detailed vocabulary presented here.

The Structure of the Neuron

The human brain contains approximately 100 billion neurons (Williams & Herrup, 1988). A neuron consists of:

• Dendrites: Receive information from other neurons; the main source of input.

• Soma: The cell body contains the nucleus and genetic information and directs protein synthesis.

• Axon: Carries the action potential to other neurons; the main source of output.

Synapse

The synapse is the point of close contact between the axon of one neuron and the dendrite of another. The axon is covered with a myelin sheath, which allows for rapid signal transmission. The axon splits and synapses with several other neurons. The end of the axon contains a terminal button (presynaptic) that forms synapses with spines (protrusions) on the dendrites (postsynaptic).

The synaptic gap or synaptic cleft is a small space (approximately $5 <br>m$) between the presynaptic terminal button and the postsynaptic dendritic spine. A dime is $1.35 <br>m$ (millimeter) thick, which equates to $1,350,000 <br>m$. The presynaptic terminal button contains synaptic vesicles which contain neurotransmitters. Neurotransmitters are released, cross the synaptic gap, and activate ion channels on the postsynaptic spine by binding to receptor sites.

Types of Cells in the Brain

Types of Neurons

• Sensory neurons receive information from the world.

• Motor neurons initiate movement and behavior.

• Interneurons process sensory input, plan behavioral responses, and connect to motor neurons.

Neuron structures:

• Unipolar neurons: one axon, no dendrites; transmit physiological information (e.g., body temperature).

• Bipolar neurons: one axon, one dendrite; involved in sensory perception (e.g., light in the retina).

• Multipolar neurons: one axon, many dendrites; communicate sensory and motor information. Pyramidal neurons are a prominent type, named for their soma's triangular shape (Furtak, Moyer, & Brown, 2007).

Glia Cells

Glia cells support neurons. Oligodendroglia form myelin sheaths around axons (Simons & Trotter, 2007). Microglia and astrocytes digest debris, provide nutritional support, and regulate the extracellular fluid's ionic composition. Glial cells do not participate in communication between cells in the same fashion as neurons do.

Communication Within and Between Neurons

There are two stages of electrochemical action in neurons:

1. Electrical conduction of dendritic input to the initiation of an action potential within a neuron.

2. Chemical transmission across the synaptic gap between the presynaptic neuron and the postsynaptic neuron of the synapse.

Resting Membrane Potential

Intracellular and extracellular fluids contain ions (electrically charged molecules). Cations are positively charged, while anions are negatively charged. Fluids contain sodium ($Na^+$), potassium ($K^+$), chloride ($Cl^-$), and anions ($A^-$).

The cell membrane separates the cell from extracellular fluid. Ion channels allow ions to pass through the membrane. Ions have different concentrations and electrical charges inside versus outside the cell. Diffusion and electrostatic pressure maintain a steady state.

• Diffusion: Molecules move from high to low concentration areas.

• Electrostatic pressure: Like charges repel, and opposite charges attract.

The equilibrium potential is when diffusion and electrostatic pressure are equal and opposite, resulting in no ion flow.

Resting membrane potential is based on the collective force on several ions and is approximately $-70 <br>V$ relative to the extracellular fluid.

Voltages of batteries and electrical outlets range from $1.5$ to $240 <br>V$.

Ion behavior

1. Anions ($A^-$): Concentrated inside, contribute to the negative charge. Impermeable to the membrane. Diffusion and electrostatic pressure do not determine its concentration. No ion channels allow for ($A^-$) to move between the intracellular and extracellular fluid.

2. Potassium ($K^+$): High concentration inside. The cell membrane is very permeable to ($K^+$) at rest, but potassium remains in high concentrations inside the cell. Diffusion pushes ($K^+$) outside, while electrostatic pressure pushes ($K^+$) inside. These forces oppose each other.

3. Chloride ($Cl^-$): High concentration outside. The cell membrane is also very permeable to chloride at rest, but chloride remains in high concentration outside the cell.
   Diffusion pushes ($Cl^-$) inside, while electrostatic pressure pushes ($Cl^-$) outside. These forces oppose each other, similar to ($K^+$).

4. Sodium ($Na^+$): High concentration outside. The cell membrane is not very permeable to sodium at rest. Diffusion and electrostatic pressure both push ($Na^+$) inside. However, ($Na^+$) cannot permeate the cell membrane and remains in high concentration outside the cell.

The sodium-potassium pump uses ATP to pump 3 ($Na^+$) ions out for every 2 ($K^+$) ions in. The small amounts of ($Na^+$) inside the cell are removed by a sodium-potassium pump, which uses the neuron’s energy ($ATP$) to pump $3 <br>umber Na^+$ ions out of the cell in exchange for bringing $2 <br>umber K^+$ ions inside the cell.

Action Potential

Electrical Signals

Hodgkin and Huxley's work (Nobel Prize in Medicine in 1963) revealed electrical signals in neurons (Hodgkin & Huxley, 1952). They studied the giant axon of squids, which is roughly 100 times larger than that of axons in the mammalian brain, making it much easier to see. Activation of the giant axon is responsible for a withdrawal response the squid uses when trying to escape from a predator. The large axon size is no mistake in nature’s design; it allows for very rapid transmission of an electrical signal, enabling a swift escape motion in the squid from its predators.

Applying an electrical stimulus to the axon results in an action potential (a large, transient electrical current).

Action Potential Defined

An action potential is an all-or-nothing response that involves a change in charge (depolarization) from the resting membrane potential ($-70 <br>umber mV$) in a positive direction.

The threshold of excitation (typically around $-50 <br>umber mV$) must be reached to initiate an action potential.

Postsynaptic Potentials

Neurons receive input that causes fluctuations in membrane potentials:

1. Excitatory postsynaptic potentials (EPSPs): Depolarizing current, making the membrane potential more positive and closer to the threshold of excitation.

2. Inhibitory postsynaptic potentials (IPSPs): Hyperpolarizing current, making the membrane potential more negative and further from the threshold of excitation.

EPSPs and IPSPs summate (add together) in time and space. IPSPs make the membrane potential more negative (amount depends on the strength of the IPSPs). EPSPs make the membrane potential more positive (amount depends on the strength of the EPSPs).

Two small EPSPs at the same time and synapse result in a large EPSP. A small EPSP and IPSP at the same time and synapse cancel each other out.

Unlike the action potential, EPSPs and IPSPs are graded potentials (varying in strength) with changes in voltage between $0.1$ to $40 <br>umber mV$.

Summation

If the summation of EPSPs is strong enough to depolarize the membrane potential to reach the threshold of excitation, then it initiates an action potential. The action potential travels down the axon to the terminal button, triggering the release of neurotransmitters into the synaptic gap. These neurotransmitters cause EPSPs and IPSPs in the postsynaptic dendritic spines of the next cell.

Neurotransmitters bind to ionotropic receptors (receptors on ion channels) on the post-synaptic dendritic spine in a lock-and-key fashion. Ionotropic receptors are receptors on ion channels that open, allowing some ions to enter or exit the cell, depending upon the presence of a particular neurotransmitter. The type of neurotransmitter and the permeability of the ion channel activated will determine if an EPSP or IPSP occurs in the dendrite of the post-synaptic cell. EPSPs and IPSPs summate and the process repeats in another cell.

Change in Membrane Potential During an Action Potential

When the cell depolarizes and reaches the threshold of excitation, voltage-dependent ($Na^+$) channels open. Voltage-dependent ion channel is a channel that opens, allowing some ions to enter or exit the cell, depending upon when the cell reaches a particular membrane potential.

Both diffusion and electrostatic pressure push ($Na^+$) inside the cell. The inside of the cell becomes very positively charged ($+40 <br>umber mV$). The Na+ channels close and become refractory (cannot reopen until the cell returns to the resting membrane potential). Thus, a new action potential cannot occur during the refractory period. The refractory period ensures the action potential moves in one direction down the axon, away from the soma.

As the cell depolarizes, voltage-dependent ($K^+$) channels open. With the cell very positive (depolarized) and high intracellular ($K^+$) concentration, both diffusion and electrostatic pressure drive $K^+$ outside of the cell. The movement of ($K^+$) out of the cell causes the cell potential to return back to the resting membrane potential, the falling or hyperpolarizing phase of the action potential. A short hyperpolarization occurs partially due to the gradual closing of the ($K^+$) channels.

Na+ channels close, and electrostatic pressure continues to push ($K^+$) out of the cell. The sodium-potassium pump pushes ($Na^+$) out of the cell. The cell returns to the resting membrane potential, and excess extracellular ($K^+$) diffuses away. This exchange of ($Na^+$) and ($K^+$) ions happens rapidly (less than $1 <br>umber msec$).

Saltatory Conduction

The action potential travels in a wave-like motion down the axon until it reaches the terminal button. Only ion channels in close proximity to the action potential are affected.

Axons are covered in myelin, with gaps called nodes of Ranvier. Myelin insulates the axon and prevents fluid between the myelin and cell membrane. Under the myelin, when the ($Na^+$) and ($K^+$) channels open, no ions flow between the intracellular and extracellular fluid, saving energy. Under the myelin, the action potential degrades some but is still large enough in potential to trigger a new action potential at the next node of Ranvier. Thus, the action potential actively jumps from node to node; this process is known as saltatory conduction.

In the presynaptic terminal button, the action potential triggers the release of neurotransmitters (see Figure 3). Neurotransmitters cross the synaptic gap and open subtypes of receptors in a lock-and-key fashion (see Figure 3). Depending on the type of neurotransmitter, an EPSP or IPSP occurs in the dendrite of the post-synaptic cell. Neurotransmitters that open ($Na^+$) or calcium ($Ca^+$) channels cause an EPSP, e.g., NMDA receptors activated by glutamate. Neurotransmitters that open ($Cl^-$) or ($K^+$) channels cause an IPSP, e.g., GABA receptors activated by GABA.

Once EPSPs and IPSPs occur in the postsynaptic site, the process cycles on. Neurotransmitters that do not bind to receptors are broken down by enzymes or glial cells, or they are taken back into the presynaptic terminal button in a process called reuptake.

References

De Carlos, J. A., & Borrell, J. (2007). A historical reflection of the contributions of Cajal and Golgi to the foundations of neuroscience. Brain Res Rev, 55(1), 8-16. doi: 10.1016/j. brainresrev.2007.03.010

Furtak, S. C., Moyer, J. R., Jr., & Brown, T. H. (2007). Morphology and ontogeny of rat perirhinal cortical neurons. J Comp Neurol, 505(5), 493-510. doi: 10.1002/cne.21516

Grant, G. (2007). How the 1906 Nobel Prize in Physiology or Medicine was shared between Golgi and Cajal. Brain Res Rev, 55(2), 490-498. doi: 10.1016/j.brainresrev.2006.11.004

Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol, 117(4), 500-544.

Lopez-Munoz, F., Boya, J., & Alamo, C. (2006). Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramon y Cajal. Brain Res Bull, 70(4-6), 391-405. doi: 10.1016/j.brainresbull.2006.07.010

Pasternak, J. F., & Woolsey, T. A. (1975). On the "selectivity" of the Golgi-Cox method. J Comp Neurol, 160(3), 307-312. doi: 10.1002/cne.901600304

Ramón y Cajal, S. (1911). Histology of the nervous system of man and vertebrates. New York, NY: Oxford University Press.

Simons, M., & Trotter, J. (2007). Wrapping it up: the cell biology of myelination. Curr Opin Neurobiol, 17(5), 533-540. doi: 10.1016/j.conb.2007.08.003

Smit, G. J., & Colon, E. J. (1969). Quantitative analysis of the cerebral cortex. I. Aselectivity of the Golgi-Cox staining technique. Brain Res, 13(3), 485-510.

Williams, R. W., & Herrup, K. (1988). The control of neuron number. Annu Rev Neurosci, 11, 423-453. doi: 10.1146/annurev.ne.11.030188.002231