44 Neurons and Nervous Systems

44 Nervous Systems: Cells and Functions Neurons: Generating and Conducting Nerve Impulses Neurons, Synapses, and Communication

44 Nervous Systems: Cells and Functions Neurons are specialized cells of the nervous system that receive, encode, and transmit information. Neurons with their support cells (glial cells) make up nervous systems. Information is received by sensory cells and converted or transduced into electrical signals that are transmitted and processed by neurons. To cause behavioral or physiological responses, a nervous system communicates these signals to effectors, such as muscles and glands.

44 Nervous Systems: Cells and Functions Simple animals process information with a simple network of neurons (nerve net) that does little more than provide direct lines of communication from sensory cells to effectors. The next level of nervous system complexity includes clusters of neurons called ganglia. Frequently one pair of ganglia is larger and more central and is given the designation brain.

Figure 44.1 Nervous Systems Vary in Size and Complexity (Part 1)

44 Nervous Systems: Cells and Functions In vertebrates, most of the cells of the nervous system are found in the brain and the spinal cord, which together are called the central nervous system (CNS). Information is transmitted from sensory cells to the CNS and from the CNS to effectors via neurons, which extend or reside outside of the brain and spinal cord. Neurons and supporting cells found outside the CNS are called the peripheral nervous system.

Figure 44.1 Nervous Systems Vary in Size and Complexity (Part 2)

44 Nervous Systems: Cells and Functions Neurons function similarly in animals as different as squids and humans. The neuron’s plasma membrane generates electrical signals called nerve impulses (or action potentials) and conducts the signals from one location on a cell to the most distant reaches of that cell. Most neurons have four regions: a cell body, dendrites, an axon, and axon terminals.

44 Nervous Systems: Cells and Functions The cell body contains the nucleus and most of the cell’s organelles. Many projections sprout from the cell body; most of them are dendrites, which bring information from other neurons or sensory cells to the cell body.

44 Nervous Systems: Cells and Functions The axon usually carries information away from the cell body. Axons conduct information to target cells, which can be other neurons, muscle cells, or gland cells. At its end, the axon divides into many fine nerve endings. At the tip of each nerve ending is a swelling called the axon terminal. The axon terminal is positioned very close to the target cell. At the axon, terminal nerve impulses cause the release of neurotransmitters (chemical messengers) into the synapse.

Figure 44.2 Neurons (Part 1)

44 Nervous Systems: Cells and Functions Variation between different types of neurons is considerable. Length of the axon differs in different cell types. Some axons can be very long.

Figure 44.2 Neurons (Part 2)

Figure 44.2 Neurons (Part 3)

44 Nervous Systems: Cells and Functions Some glial cells physically support and orient neurons. Others provide insulation for axons. Schwann cells are a type of glial cell that wraps around the axons of neurons in the peripheral nervous system, providing electrical insulation. Oligodendrocytes have a similar function for axons in the CNS. Myelin is the covering produced by Schwann cells and oligodendrocytes.

Figure 44.3 Wrapping Up an Axon

44 Nervous Systems: Cells and Functions Glial cells supply neurons with nutrients. Some consume foreign particles, and some maintain ionic balance around neurons. Some glial cells communicate electrically through gap junctions. Glial cells called astrocytes contribute to the blood–brain barrier, which protects the brain from toxic chemicals in the blood. Astrocytes surround the smallest blood vessels in the brain. They are permeable to fat-soluble molecules such as alcohol.

44 Nervous Systems: Cells and Functions It is important to remember that nervous systems depend on neurons working together. The simplest neural network consists of three cells: a sensory neuron connected to a motor neuron connected to a muscle cell. Most neuronal networks are more complex. The human brain has an estimate neurons and synapses. The neurons and synapses in the human brain are divided into thousands of distinct but interacting networks that function in parallel.

44 Neurons: Generating and Conducting Nerve Impulses The difference in voltage across the plasma membrane of a neuron is called its membrane potential. In an unstimulated neuron, the voltage difference is called a resting potential. Membrane potentials can be measured with electrodes. The membrane potential of a resting axon is about –60 millivolts (mV). The inside of the cell is more negative than the outside.

Figure 44.4 Measuring the Resting Potential (Part 1)

Figure 44.4 Measuring the Resting Potential (Part 2)

44 Neurons: Generating and Conducting Nerve Impulses A neuron is sensitive to chemical or physical factors that cause a change in the resting potential. An action potential is the sudden and rapid reversal in voltage across a portion of the plasma membrane. For 1 to 2 milliseconds, the inside of the cell becomes more positive than the outside. Nerve impulses are action potentials that travel along axons.

44 Neurons: Generating and Conducting Nerve Impulses Voltage (potential or electric charge difference) is the tendency for electrically charged particles like electrons or ions to move between two points. Electrical charges move across cell membranes not as electrons, but as charged ions. The major ions that carry electric charges across the plasma membranes of neurons are sodium (Na + ), chloride (Cl – ), potassium (K + ), and calcium (Ca 2+ ). Ions with opposite charges attract one another; ions with like charges repel.

44 Neurons: Generating and Conducting Nerve Impulses Ion pumps use energy to move ions or other molecules against their concentration gradients. The major ion pump in neuronal membranes is the sodium–potassium pump, which expels Na + ions from the cell, exchanging them for K + ions from outside the cell. This keeps the concentration of K + greater inside the cell than outside. Ion channels are pores formed by proteins in the lipid bilayer that selectively allow ions to pass through.

Figure 44.5 Ion Pumps and Channels

44 Neurons: Generating and Conducting Nerve Impulses Potassium channels are the most common open channels in the plasma membranes of resting neurons, and resting neurons are more permeable to K + than any other ion. The sodium–potassium pump keeps K + concentration high inside the cell, but K + can diffuse out the open channels. The membrane potential at which the tendency of K + ions to diffuse into the cell is equal to their tendency to diffuse out is called the potassium equilibrium potential.

Figure 44.6 Open Potassium Channels Create the Resting Potential

44 Neurons: Generating and Conducting Nerve Impulses The value of the potassium equilibrium potential can be calculated with the Nernst equation. The Nernst equation predicts a resting potential of about –84 mV. The actual resting potential is a little less negative because resting neurons are also slightly permeable to other ions, such as Na + and Cl –.

Figure 44.7 The Nernst Equation

44 Neurons: Generating and Conducting Nerve Impulses Many ion channels in the plasma membranes of neurons are gated; they open under some conditions but close under other conditions. Voltage-gated channels open or close in response to a change in the voltage across a plasma membrane. Chemically gated channels open or close depending on the presence or absence of a specific chemical that binds to the channel protein.

44 Neurons: Generating and Conducting Nerve Impulses When the inside of a neuron becomes less negative in comparison to its resting condition, its plasma membrane is said to be depolarized. Conversely, when the inside of a neuron becomes more negative in comparison to its resting condition, its plasma membrane is said to be hyperpolarized. Opening and closing of ion channels, which result in changes in the polarity of the plasma membrane, are the basic mechanisms by which neurons respond to stimuli.

Figure 44.8 Membranes Can Be Depolarized or Hyperpolarized

44 Neurons: Generating and Conducting Nerve Impulses Local changes in membrane potential cause a flow of electrically charged ions, which tends to spread the change in membrane potential to adjacent regions of the membrane. This flow of ions is an electrical current. It does not travel very far before it diminishes because the membranes are permeable to ions. Hence, the axon does not transmit information as a continuous flow of electrical current. Local flow of electric current is part of the mechanism that generates the signals that axons do transmit: action potentials.

44 Neurons: Generating and Conducting Nerve Impulses An action potential is a sudden and major change in membrane potential that lasts for about 1–2 milliseconds. Action potentials are conducted along axons at speeds of up to 100 meters per second. If the membrane potential of an axon is measured when an action potential passes, the voltage changes from the resting potential of –60 mV to +50 mV, then rapidly returns to the resting potential.

44 Neurons: Generating and Conducting Nerve Impulses Voltage-gated sodium channels are primarily responsible for action potentials. At resting potential, most of the sodium channels are closed. A specific membrane potential called the threshold potential opens voltage-gated ion channels. During the transmission of an action potential, the sodium channels stay open for less than a millisecond; in that time sodium rushes into the cell. The opening of sodium channels causes the rising phase (spike) of the action potential.

Figure 44.9 The Course of an Action Potential

44 Neurons: Generating and Conducting Nerve Impulses Potassium channels open more slowly than the sodium channels and stay open longer; this allows potassium ions to carry excess positive charges out of the axon. Potassium channels thus help the plasma membrane return to its resting potential.

44 Neurons: Generating and Conducting Nerve Impulses Another feature of voltage-gated sodium channels is that once they open and close, they can be triggered again only after a short delay of 1–2 milliseconds. This delay is the refractory period, the time when a plasma membrane cannot propagate an action potential.

44 Neurons: Generating and Conducting Nerve Impulses The concentration of K + and Na + ions on opposite sides of the plasma membrane is the “battery” that drives action potentials. Since only a small fraction of the total amount of Na + ions moves down their concentration gradient when sodium channels open, the overall ratio of K + to Na + is not changed very much. Therefore, the “battery” can be recharged without difficulty even when many action potentials are being transmitted.

44 Neurons: Generating and Conducting Nerve Impulses Action potentials travel long distances with no loss of signal. Action potentials are all-or-nothing due to the interaction between the voltage-gated sodium channels and the membrane potential. The action potential is self-regenerating because it spreads by current flow to adjacent regions of the membrane. The action potential propagates in one direction and cannot be reversed because the part of the membrane it came from is in its refractory period. Action potentials travel faster in large-diameter axons than in small-diameter axons.

Figure Action Potentials Travel along Axons (Part 1)

Figure Action Potentials Travel along Axons (Part 2)

Figure Action Potentials Travel along Axons (Part 3)

44 Neurons: Generating and Conducting Nerve Impulses In the 1940s, the neurophysiologists A. L. Hodgkin and A. F. Huxley used giant axons from squid to study the electrical properties of axonal membranes. At the time, they could only hypothesize about the existence of ion channels. Patch clamping, developed by Bert Sackmann and Erwin Neher, is a research method developed in the 1980s that allows single ion channels to be studied. A recording pipette is used to “clamp” a patch of neuron plasma membrane and measure the voltage differences when ion channels in that patch of membrane open and close.

Figure Patch Clamping

44 Neurons: Generating and Conducting Nerve Impulses In vertebrates, it is impractical to increase propagation velocity by increasing axon size because of the very large numbers of axons present. Another mechanism has evolved that increases propagation velocity. Recall that Schwann cells wrap axons in myelin. The myelin wrapper is not continuous; it has regularly spaced gaps, called nodes of Ranvier, where the axon is not covered.

44 Neurons: Generating and Conducting Nerve Impulses Myelin electrically insulates the axon (charged ions cannot cross the regions of the axon that are wrapped in myelin). Ion channels are clustered at the nodes of Ranvier. When an action potential fires at one node of Ranvier, it jumps to the next via saltatory conduction. Saltatory conduction is much faster than continuous signal propagation down unmyelinated axons because electric current travels quickly through the cytoplasm compared to the time required for ion channels to open and close.

Figure Saltatory Action Potentials (Part 1)

Figure Saltatory Action Potentials (Part 2)

44 Neurons, Synapses, and Communication Interactions among neurons depend on the synapses between cells. Electrical and chemical messages are exchanged at the synapse. The cell that sends the message is called the presynaptic cell; the cell that receives it is the postsynaptic cell. The most common type of synapse in the nervous system is the chemical synapse.

44 Neurons, Synapses, and Communication A neuromuscular junction is the synapse between a motor neuron and a muscle cell. Each axon terminal of a motor neuron is enlarged and contains many vesicles filled with chemical messenger molecules know as neurotransmitters. Acetylcholine is the neurotransmitter used by all vertebrate motor neurons. Acetylcholine is released when the vesicles fuse with the presynaptic membrane and moves into the narrow space called the synaptic cleft.

Figure Synaptic Transmission Begins with the Arrival of a Nerve Impulse

44 Neurons, Synapses, and Communication The postsynaptic membrane of a neuromuscular junction is a modified part of the muscle cell plasma membrane called a motor end plate. The motor end plate contains acetylcholine-gated channels that allow both Na + and K + to pass through them. When acetylcholine binds to its receptor and opens the channel, Na + moves into the cell (since the cell is permeable to K + already) and the motor end plate is depolarized.

Figure The Acetylcholine Receptor is a Chemically Gated Channel

44 Neurons, Synapses, and Communication Voltage-gated calcium channels in the membrane of the axon terminal are activated by incoming action potentials in the neuron. Ca 2+ diffuses down its concentration gradient into the neuron. The increase in intracellular Ca 2+ in the presynaptic cell causes the vesicles containing acetylcholine to fuse with the presynaptic cell’s membrane and empty their contents into the synaptic cleft. Acetylcholine can then diffuse across the cleft and interact with the acetylcholine receptors on the postsynaptic cell.

44 Neurons, Synapses, and Communication Motor end plates have very few voltage-gated sodium channels; therefore, they do not fire action potentials. The rest of the muscle cell has voltage-gated sodium channels. If a motor neuron releases sufficient amounts of neurotransmitter to depolarize a motor end plate enough to bring the surrounding membrane to the threshold potential, an action potential will be fired. About 100 acetylcholine vesicles, each containing about 10,000 acetylcholine molecules, must release their cargo into the synaptic cleft to cause the muscle cell to fire an action potential.

44 Neurons, Synapses, and Communication Synapses between neurons are categorized as excitatory or inhibitory depending on their response to neurotransmitter (chemical) messages. If a postsynaptic neuron responds to chemical stimulation by depolarizing, the synapse is excitatory. If the postsynaptic neuron hyperpolarizes, the synapse is inhibitory.

44 Neurons, Synapses, and Communication Gamma-amino butyric acid (GABA) and glycine are the most common inhibitory neurotransmitters in vertebrates. The postsynaptic cells at inhibitory synapses have chemically gated chloride channels. When the channels are activated, they can hyperpolarize the postsynaptic membrane and make the postsynaptic cell less likely to fire an action potential.

44 Neurons, Synapses, and Communication Neurotransmitters that depolarize the postsynaptic membrane are excitatory and bring about an excitatory postsynaptic potential (EPSP). Neurotransmitters that hyperpolarize the postsynaptic membrane are inhibitory and bring about an inhibitory postsynaptic potential (IPSP).

44 Neurons, Synapses, and Communication For most neurons, the critical area for the “decision” to fire an action potential is the axon hillock, a region of the cell body at the base of the axon. The plasma membrane of the axon hillock is not myelinated and has many voltage-gated ion channels. Inputs from the synapses are conducted through the cell body. If the resulting combined potential depolarizes the axon hillock to threshold, the axon fires an action potential. Synapses closer to the cell body have greater influence on the axon hillock because action potentials decrease as they spread from the synapse.

Figure The Postsynaptic Neuron Sums Information (Part 1)

44 Neurons, Synapses, and Communication Excitatory and inhibitory postsynaptic potentials are summed spatially and temporally. Spacial summation adds up the simultaneous influences of synapses at different sites on the postsynaptic cell. Temporal summation adds up postsynaptic potentials generated at the same site in a rapid sequence.

Figure The Postsynaptic Neuron Sums Information (Part 2)

44 Neurons, Synapses, and Communication Synapses may also form between the axon terminals of two neurons. Such a synapse can modulate how much neurotransmitter the second neuron releases in response to action potentials traveling down its axon. This mechanism of control is called presynaptic excitation or presynaptic inhibition.

44 Neurons, Synapses, and Communication There are two types of neurotransmitter receptors: ionotropic and metabotropic. Ionotropic receptors are ion channels. Neurotransmitter binding by an ionotropic receptor causes a direct change in ion movements across the postsynaptic cell membrane. The acetylcholine receptor is an ionotropic receptor.

44 Neurons, Synapses, and Communication Metabotropic receptors induce changes in the postsynaptic cell that can lead secondarily to changes in ion channels. Postsynaptic cell responses mediated by metabotropic receptors are generally slower and longer-lasting than those induced by ionotropic receptors. Metabotropic receptors initiate an intracellular signaling process that can result in the opening or closing of ion channels. Metabotropic receptors are G protein-coupled receptors.

Figure Metabotropic Receptors Act through G Proteins

44 Neurons, Synapses, and Communication Electrical synapses, or gap junctions, are different from chemical synapses because they couple neurons electrically. The two neurons are connected by membrane proteins called connexons that form a tunnel through which ions and small molecules can pass. Transmission at electrical synapses is very fast and bidirectional (as opposed to transmission at chemical synapses, which is slower and unidirectional).

44 Neurons, Synapses, and Communication Gap junctions are less common than chemical synapses in vertebrates for several reasons:  Electrical continuity between neurons does not allow temporal summation of synaptic inputs.  An effective electrical synapse requires a large area of contact between cells.  Electrical synapses cannot be inhibitory.  Electrical synapses do not appear to be very modifiable. Thus, electrical synapses are good for rapid communication, but not for processes of integration and learning.

44 Neurons, Synapses, and Communication Many kinds of neurotransmitters are now recognized. Glutamate (excitatory), glycine and GABA (inhibitory) are the most common neurotransmitters of the CNS. A recent discovery is that two gases, carbon monoxide and nitric oxide, are used by neurons as intercellular messengers even though they do not have the characteristics of classic neurotransmitters (i.e., they do not have receptors).

44 Neurons, Synapses, and Communication The complexity of neurotransmission is increased by the fact that each neurotransmitter has multiple receptor types. The action of a neurotransmitter depends on the receptor to which it binds. Acetylcholine, for example, has nicotinic receptors (which are ionotrophic and tend to be excitatory in the CNS) and muscarinic receptors (which are metabotropic and tend to be inhibitory in the CNS).

44 Neurons, Synapses, and Communication Glutamate receptors are divided into classes depending on their differential activation by chemicals that mimic glutamate. NMDA and AMPA are examples of ionotropic glutamate receptors. Glutamate is an excitatory neurotransmitter, so activation of glutamate receptors always results in Na + entry into the neuron and depolarization. However, the timing of Na + influx for NMDA and AMPA receptors varies. AMPA receptors allow a rapid influx. NMDA receptors allow a slower and longer-lasting influx.

44 Neurons, Synapses, and Communication NMDA and AMPA work in concert. At resting potential, the NMDA receptor is blocked by a magnesium ion (Mg 2+ ). Strong depolarization of the neuron due to inputs, such as the activation of AMPA receptors, displaces Mg 2+ from the NMDA receptors, allowing Na + and Ca 2+ to pass through them when they are activated by glutamate. These properties of the NMDA receptor are probably involved in learning and memory.

Figure Two Ionotropic Glutamate Receptors

44 Neurons, Synapses, and Communication Our understanding of the way in which messages carried by action potentials can result in long-term events such as learning and memory has been affected by the discovery of a phenomenon called long-term potentiation (LTP). LTP makes a neuron more sensitive to inputs. LTP results from rapid repeated stimulation of synaptic inputs of a neuron. The size of postsynaptic response is enhanced and can last for days or weeks.

Figure Repeated Stimulation Can Cause Long-Term Potentiation (Part 1)

Figure Repeated Stimulation Can Cause Long-Term Potentiation (Part 2)

44 Neurons, Synapses, and Communication Neurotransmitter action may be terminated in several ways:  Enzymes may destroy the neurotransmitter. For example, acetylcholine is repidly broken down by acetylcholinesterase.  The neurotransmitter may diffuse away from the synaptic cleft.  The neurotransmitter may be taken up via active transport.