The Nervous System Is Composed of Cells Types of cells in the nervous system Neurons, or nerve cells are the most important part of the nervous system There are many types of neurons Glial cells provide support for neurons Microglia Astrocytes Oligodendrocytes Schwann cells Neuron doctrine states that: The brain is composed of independent cells. Information is transmitted from cell to cell across synapses.

Scale of Things

Figure 2.2 The Major Parts of the Neuron A neuron has four zones: Input zone—receives information from other cells through dendrites Integration zone—cell body (or soma) region where inputs are combined and transformed Conduction zone—single axon leads away from the cell body and transmits the electrical impulse Output zone—axon terminals at the end of the axon communicate activity to other cells

Figure 2.5 A Classification of Neurons into Three Principal Types Neurons are classified by shape, size, or function: Multipolar neurons–one axon, many dendrites–most common type Bipolar neurons–one axon, one dendrite Monopolar neurons–a single extension branches in two directions, forming a receptive pole and an output zone Large neurons: Have more complex inputs and outputs Cover greater distances Convey information more rapidly

Figure 2.7 Glial Cells Glial cells support neuronal activity: Astrocytes—star-shaped cells with many processes that receive neuronal input and monitor activity Microglial cells, or microglia—small cells that remove debris from injured cells Myelination—the process in which glial cells wrap axons with a fatty sheath, myelin, to insulate and speed conduction Nodes of Ranvier—gaps between sections of myelin where the axon is exposed Multiple sclerosis—a demyelinating disease Oligodendrocytes are glial cells that form myelin sheath in the brain and spinal cord. Schwann cells provide myelin to cells outside the brain and spinal cord. Glial cells respond to injury by edema, or swelling, and are also susceptible to tumors.

Neuron Classification By Function into three groups, which is all but useless Sensory Neurons Interneurons Motor Neurons By Structure into three groups, not much better Unipolar: dendrite and axon emerging from same process. Bipolar: axon and single dendrite on opposite ends of the soma. Multipolar: more than two dendrites: Golgi I: neurons with long-projecting axonal processes; examples are pyramidal cells, Purkinje cells, and anterior horn cells. Golgi II: neurons whose axonal process projects locally; the best example is the granule cell. Most neurons are named as they are discovered which is not classification and results in a very long list There currently is no useful classification system for neurons

Box 2.1 Neuroanatomical Methods Provide Ways to Make Sense of the Brain Visualizing structures in the brain: Golgi stains fill the whole cell, including details, but only stain a small proportion of neurons. Fluorescent molecule injections give a similar result. Nissl stains outline all cell bodies because the dyes are attracted to RNA, which encircles the nucleus. Autoradiography shows the distribution of radioactive chemicals in tissues. Immunocytochemistry can detect a protein in tissue: An antibody binds to the protein. Chemical treatments make the antibody visible. In situ hybridization uses complementary radioactive probes to find neurons with a specific mRNA sequence. Immediate early genes (IEGs) such as c-fos are expressed when cells first become active. Tracing Pathways in the Brain: Anterograde labeling uses radioactive molecules taken up by the cell and then transported to the axon tips. Retrograde labeling uses horseradish peroxidase (HRP)—it is taken up in the axon terminals and transported to the cell bodies, then visualized through chemical reactions.

Figure 2.1 Nineteenth-Century Drawings of Neurons Another example of neuron diversity from the work of Cajal whom realized the importance of this diversity for function of brain circuits. Diversity increases the capacity to process information and adapt to new information i.e. new experiences. Visualizing structures in the brain: Golgi stains fill the whole cell, including details, but only stain a small proportion of neurons. Fluorescent molecule injections give a similar result. Nissl stains outline all cell bodies because the dyes are attracted to RNA, which encircles the nucleus.

Retinal Circuits Retinal Circuits http://webvision.med.utah.edu/book/part-vi-development-of-cell-types-and-synaptic-connections-in-the-retina/development-of-cell-types-and-synaptic-connections-in-the-retina/

Figure 2.3 Variety in the Form of Nerve Cells Note the diversity in shape and size of these neurons, it is very difficult to classify neurons based on morphology. Neurons are named as they are discovered but this is not classification.

Diversity of Neurons Thousands of different types of neurons Improves information processing Perception under a range of circumstances Flexible processing to assess unexpected things Circuit diagram of sensory neocortex Yuste lab composite diagram of circuits in the sensory neocortex

Synapses Neurons are interconnected through synapses Individual neurons do not have specific behavioral or cognitive functions neurons connected into a circuit have function The neuronal cell body and dendrites receive information across synapses. Dendrites have a branched arborization pattern to facilitate contacts. Information is transmitted from the presynaptic neuron to the postsynaptic neuron. (Mostly) There are chemical signals from postsynaptic neuron to presynaptic neuron called “retrograde” which is some sort of feedback signal

Figure 2.6 Synapses

EM of Chemical synapse mitochondria Active Zone Figure 5.3, Bear, 2001

EM of synapses on cell body

A segment of pyramidal cell dendrite from stratum radiatum (CA1) with thin, stubby, and mushroom-shaped spines from rat hippocampus. Found at Synapse Web http://synapses.clm.utexas.edu/anatomy/compare/compare.stm Dendritic spines are studded on the dendrites and increase surface area. The property of neural plasticity in dendritic spines allows their number and structure to be rapidly altered by experience.

Neurophysiology The electrical and chemical processes within neurons An action potential is a rapid electrical signal that travels along the axon of a neuron. A neurotransmitter is a chemical messenger between neurons. Electrical and chemical processes work together Chemistry produces the electrical activity Electrical activity modulates the chemistry

Figure 3.3 The Ionic Basis of the Resting Potential

Fig 3.4 Distribution of Ions The cell membrane is a lipid bilayer, with two layers of lipid molecules. Ion channels are proteins that span the membrane and allow ions to pass. Gated ion channels open and close in response to voltage changes, chemicals, or mechanical action Some channels are open all the time and allow only potassium ions (K+) to cross. The neuron shows selective permeability to (K+)–it can enter or leave the cell freely. Two opposing forces drive ion movement: Diffusion causes ions to flow from areas of high to low concentration, along their concentration gradient. Electrostatic pressure causes ions to flow towards oppositely charged areas. Fig 3.4

Fig 3.6 Action Potential Mediated by Voltage-Gated Na Channels Action potentials are brief but large changes in membrane potential. They originate in the axon hillock and are propagated along the axon. Patterns of action potentials carry information to postsynaptic targets. Hyperpolarization is an increase in membrane potential–the interior of the membrane becomes even more negative. Depolarization is a decrease in membrane potential–the interior of the cell becomes less negative. A hyperpolarizing stimulus produces a response that passively follows the stimulus. The greater the stimulus the greater the response–the change in potential is called a graded response. Local potential–as the potential spreads across the membrane, it diminishes as it moves away from the point of stimulation A depolarizing stimulus If the membrane reaches the threshold–about –40 mV–it triggers an action potential. The membrane potential reverses and the inside of the cell becomes positive. All-or-none property of action potentials: the neuron fires at full amplitude or not at all–does not reflect increased stimulus strength Action potentials increase in frequency with increased stimulus strength. Afterpotentials–changes in membrane potential after action potentials Action potentials are produced by the movement of Na+ ions into the cell. At the peak the concentration gradient pushing Na+ ions in equals the positive charge driving them out. Membrane shifts briefly from a resting state to an active state, and back. Voltage-gated Na+ channels open in response to the initial depolarization. More voltage-gated channels open and more Na+ ions enter. This continues until the membrane potential reaches the Na+ equilibrium potential of +40 mV. As the inside of the cell becomes more positive, voltage-gated K+ channels open. K+ moves out and the resting potential is restored. Refractory period–only some stimuli can produce an action potential Absolute refractory phase–no action potentials are produced Relative refractory phase–only strong stimulation can produce an action potential

Ion Channels The cell membrane is a lipid bilayer, with two layers of lipid molecules. Ion channels are proteins that span the membrane and allow ions to pass. There are many types of ion channels Usually classified based on gating and type of ion Gating Voltage-Gated ion channels open and close in response to membrane potential. Ligand-gated ion channels open or close depending on binding of ligands to the channel Type of Ion Sodium (Na) Potassium (K) Chloride (Cl) Calcium (Ca)

FIGURE 2 | General structural topology of voltage-gated ion channels. The distribution and targeting of neuronal voltage-gated ion channels Helen C. Lai and Lily Y. Jan Nature Reviews Neuroscience 7, 548-562 (July 2006)

Voltage-gated sodium channel Function Animation of voltage gated Na channel, when the outside is depolarized the gate on the inside of the channel opens. Voltage-gated sodium channel Function

Potassium channel in membrane You Tube video Potassium Channels Ion channels are very specific in their function: K+ channels are lined with oxygen atoms that mimic water molecules. K+ ions pass through this selectivity filter more easily than Na+. Channelopathy–genetic abnormality of ion channels Potassium channel in membrane You Tube video

Action Potential Animations Action Potential Animation You Tube video Action Potential animation, advanced with detailed explanation You Tube video

Fig 3.8a Conduction along Axons Action potentials are regenerated along the axon—each adjacent section is depolarized and a new action potential occurs. Action potentials travel in one direction because of the refractory state of the membrane after a depolarization.

Fig 3.8b Conduction along Axons Conduction velocity—the speed of propagation of action potentials—varies with diameter Nodes of Ranvier—small gaps in the insulating myelin sheath Saltatory conduction—the axon potential travels inside the axon and jumps from node to nod