The Brain Overview: Command and Control Center The human brain contains an estimated 100 billion nerve cells, or neurons Each neuron may communicate with thousands of other neurons

Functional magnetic resonance imaging is a technology that can reconstruct a three-dimensional map of brain activity Figure 48.1

The results of brain imaging and other research methods reveal that groups of neurons function in specialized circuits dedicated to different tasks

Nervous systems Nervous systems consist of circuits of neurons and supporting cells All animals except sponges have some type of nervous system What distinguishes the nervous systems of different animal groups is how the neurons are organized into circuits

Organization of Nervous Systems The simplest animals with nervous systems, the cnidarians Have neurons arranged in nerve nets Nerve net (a) Hydra (cnidarian)

(b) Sea star (echinoderm) Sea stars have a nerve net in each arm Connected by radial nerves to a central nerve ring Nerve ring Radial nerve (b) Sea star (echinoderm)

(c) Planarian (flatworm) In relatively simple cephalized animals, such as flatworms A central nervous system (CNS) is evident Eyespot Brain Nerve cord Transverse nerve (c) Planarian (flatworm)

(e) Insect (arthropod) Annelids (worms) and arthropods (crustacenas, insects)h ave segmentally arranged clusters of neurons called ganglia These ganglia connect to the CNS and make up a peripheral nervous system (PNS) Brain Ventral nerve cord Segmental ganglion Ventral nerve cord Segmental ganglia (d) Leech (annelid) (e) Insect (arthropod)

Longitudinal nerve cords Nervous systems in molluscs correlate with the animals’ lifestyles. Sessile molluscs have simple systems whereas more active, predatory molluscs have more sophisticated systems. Anterior nerve ring Longitudinal nerve cords Ganglia Brain (f) Chiton (mollusc) (g) Squid (mollusc)

(h) Salamander (chordate) In vertebrates the central nervous system consists of a brain and dorsal spinal cord The PNS connects to the CNS Figure 48.2h Brain Spinal cord (dorsal nerve cord) Sensory ganglion (h) Salamander (chordate)

Information Processing Nervous systems process information in three stages Sensory input, integration, and motor output Figure 48.3 Sensor Effector Motor output Integration Sensory input Peripheral nervous system (PNS) Central nervous system (CNS)

Sensory neurons transmit information from sensors that detect external stimuli and internal conditions Sensory information is sent to the CNS where interneurons integrate the information Motor output leaves the CNS via motor neurons which communicate with effector cells

The three stages of information processing Are illustrated in the knee-jerk reflex Figure 48.4 Sensory neurons from the quadriceps also communicate with interneurons in the spinal cord. The interneurons inhibit motor neurons that supply the hamstring (flexor) muscle. This inhibition prevents the hamstring from contracting, which would resist the action of the quadriceps. The sensory neurons communicate with motor neurons that supply the quadriceps. The motor neurons convey signals to the quadriceps, causing it to contract and jerking the lower leg forward. 4 5 6 The reflex is initiated by tapping the tendon connected to the quadriceps (extensor) muscle. 1 Sensors detect a sudden stretch in the quadriceps. 2 Sensory neurons convey the information to the spinal cord. 3 Quadriceps muscle Hamstring muscle Spinal cord (cross section) Gray matter White matter Cell body of sensory neuron in dorsal root ganglion Sensory neuron Motor neuron Interneuron

Neuron Structure Most of a neuron’s organelles are located in the cell body. Neurons have dendrites which are highly branched extensions that receive signals from other neurons. Figure 48.5 Dendrites Cell body Nucleus Axon hillock Axon Signal direction Synapse Myelin sheath Synaptic terminals Presynaptic cell Postsynaptic cell

The axon is a long extension of a dendrite that transmits signals to other cells at synapses. The axon may be covered with a myelin sheath, which facilitates signal transmission.

Supporting Cells (Glia) Glia are supporting cells that are essential for the structural integrity of the nervous system and for the normal functioning of neurons. In the CNS, astrocytes provide structural support for neurons and regulate the extracellular concentrations of ions and neurotransmitters

Astrocytes Figure 48.7 50 µm

Oligodendrocytes (in the CNS) and Schwann cells (in the PNS) are glia that form the myelin sheaths around the axons of many vertebrate neurons Myelin sheath Nodes of Ranvier Schwann cell Nucleus of Schwann cell Axon Layers of myelin Node of Ranvier 0.1 µm Figure 48.8

The nervous system transmits information using a combination of electrical and chemical signals. Signals are transmitted along neurons electrically and signals are transmitted between neurons at synapses chemically.

How a neuron delivers a signal Synapse Cell Body Axon Dendrites Electrical Chemical

Membrane potentials Ion pumps and ion channels maintain the resting potential of a neuron Across its plasma membrane, every cell has a voltage called a membrane potential The inside of a cell is negative relative to the outside

Basic Electrical Concepts Like charges repel one another. Opposite charges attract one another. Because of the attractive force between positive and negative charges, energy must be expended and work must be done to separate them. Conversely, if positive and negative charges are allowed to come together, energy is liberated, and this energy can be used to perform work. Thus, when positive and negative charges are separated, they have the potential to perform work.

Basic Electrical Concepts Potential is measured as voltage (1mV = 0.001V). Voltage is measured between two points (potential). Current is measured as the amount of charge moving between two points.

The membrane potential of a cell can be measured Figure 48.9 APPLICATION Electrophysiologists use intracellular recording to measure the membrane potential of neurons and other cells. TECHNIQUE A microelectrode is made from a glass capillary tube filled with an electrically conductive salt solution. One end of the tube tapers to an extremely fine tip (diameter < 1 µm). While looking through a microscope, the experimenter uses a micropositioner to insert the tip of the microelectrode into a cell. A voltage recorder (usually an oscilloscope or a computer-based system) measures the voltage between the microelectrode tip inside the cell and a reference electrode placed in the solution outside the cell. Microelectrode Reference electrode Voltage recorder –70 mV

The Resting Potential The resting potential is the membrane potential of a neuron that is not transmitting signals.

In all neurons, the resting potential depends on the ionic gradients that exist across the plasma membrane CYTOSOL EXTRACELLULAR FLUID [Na+] 15 mM [K+] 150 mM [Cl–] 10 mM [A–] 100 mM [Na+] 150 mM [K+] 5 mM [Cl–] 120 mM – + Plasma membrane Figure 48.10

Understanding resting potential The concentration of Na+ is higher in the extracellular fluid than inside the cell, while the opposite is true for K+. The inside of the cell contains negatively charged molecules such as proteins and amino acids and negatively charged ions such as phosphate and sulfate. The cell membrane has different permeabilities for different ions and permeability for K+ is higher than for Na+.

Because K+ ions are much more concentrated inside the nerve cell than outside, they diffuse out of the cell. Negatively charged ions cannot follow as there are no channels for them to flow through. The loss of positively charged K+ ions means there is net negative charge inside the cell.

The net flow of K+ ions will continue and the negative charge will increase until the difference in charge between the inside and outside of the cell (which attracts K+ ions back into the cell) balances the effect of the concentration gradient for K+, which is causing K+ ions to flow out. If it was only the flow of K+ ions that established the cell’s resting potential then a resting potential of -85mV would be established.

However, there is a trickle of Na+ ions that flows into the cell down its concentration gradient in the opposite direction to the flow of K+ ions. This flow of Na+ is counteracted by active pumping of Na+ out of the cell, but even so the resting potential of a neuron is typically apprximately -70mV, rather than -85mV.

Excitable cells All cells have a membrane potential, but only certain cells such as neurons and muscle cells can change their membrane potentials in response to a stimulus. Such cells are called excitable cells. Special ion channels called gated channels allow neurons to change their membrane potential.

Gated Ion Channels Gated ion channels open or close in direct response to membrane stretch or the binding of a specific ligand or in response to a change in the membrane potential. How the resting potential changes, depends on the gated channels that open.

Gated Ion Channels Opening K+ channels will increase the flow of K+ out of the cell and hyperpolarize the cell making the potential more negative.

Membrane potential (mV) Hyperpolarization Figure 48.12a +50 –50 –100 Time (msec) 0 1 2 3 4 5 Threshold Resting potential Hyperpolarizations Membrane potential (mV) Stimuli (a) Graded hyperpolarizations produced by two stimuli that increase membrane permeability to K+. The larger stimulus produces a larger hyperpolarization.

Gated Ion Channels Opening Na+ channels, in contrast, will allow Na+ to flow into the cell and will depolarize the cell reducing the negative charge and even making it positive.

Membrane potential (mV) Depolarization Figure 48.12b +50 –50 –100 Time (msec) 0 1 2 3 4 5 Threshold Resting potential Depolarizations Membrane potential (mV) Stimuli (b) Graded depolarizations produced by two stimuli that increase membrane permeability to Na+. The larger stimulus produces a larger depolarization.

Hyperpolarization and depolarization are both called graded potentials because the magnitude of the change in membrane potential varies with the strength of the stimulus

Production of Action Potentials In most neurons, however, depolarizations are graded only up to a certain membrane voltage, called the threshold. A stimulus strong enough to produce a depolarization that reaches the threshold triggers a different type of response, called an action potential.

Action potential Figure 48.12c Stronger depolarizing stimulus +50 –50 –100 Time (msec) 0 1 2 3  4 5 6 Threshold Resting potential Membrane potential (mV) Stronger depolarizing stimulus Action potential (c) Action potential triggered by a depolarization that reaches the threshold.

Action potential An action potential is a brief all-or-none depolarization of a neuron’s plasma membrane It is the type of signal that carries information along axons.

Production of an action potential Both voltage-gated Na+ channels and voltage-gated K+ channels are involved in the production of an action potential When a stimulus depolarizes the membrane Na+ channels open, allowing Na+ to diffuse into the cell

After the Na+ have opened they close and K+ channels open. K+ flows out of the cell rapidly reversing the polarity of the cell and briefly undershooting the cell’s resting potential briefly before the resting potential is restored. During the undershoot a second action potential cannot be initiated and this time when the cell is insensitive to stimulation is called the refractory period.

Conduction of Action Potentials An action potential can be used to transmit a signal because the action potential can “travel” long distances by regenerating itself along the length of the axon. At the site where the action potential is generated, the electrical current depolarizes the neighboring region of the axon membrane. Rather like tipping one in a line of standing dominoes the effect of an action potential is transmitted along the length of an axon.

Figure 48.14 – + Na+ Action potential K+ Axon An action potential is generated as Na+ flows inward across the membrane at one location. 1 2 The depolarization of the action potential spreads to the neighboring region of the membrane, re-initiating the action potential there. To the left of this region, the membrane is repolarizing as K+ flows outward. 3 The depolarization-repolarization process is repeated in the next region of the membrane. In this way, local currents of ions across the plasma membrane cause the action potential to be propagated along the length of the axon.

Direction of transmission The direction of flow is one directional because of the fact that there is a refractory period after a section of membrane depolarizes when it cannot be restimulated. This prevents the signal being sent back in the opposite direction along the axon.

Conduction Speed In many instances it is important that action potentials be transmitted quickly. The speed of transmission of an axon potential increases with the diameter of an axon because thicker axons offer proportionally less resistance to the flow of current. Thus, many invertebrates (including squid, lobsters and cockroaches) have evolved giant axons that enable them to react quickly to stimuli.

Vertebrates, however, have come up with a different solution to increasing the speed of transmission. In vertebrates axons are myelinated, insulated with a layer of membranes deposited by glial or Schwann cells. Myelin is a poor conductor and prevents the electrical signal being dissipated outside the neuron so it is more effectively and quickly transmitted along it.

Multiple Sclerosis People who suffer from multiple sclerosis have neurons in which the myelin sheaths gradually deteriorate. This disrupts nerve signal transmission and leads to progressive loss of body function.

Neurons have myelinated and unmyelinated sections Gated ion channels are concentrated in the unmyelinated sections, called the nodes of Ranvier. Action potentials jump between unmyelinated sections of neuron in a process called saltatory conduction with depolarization skipping the myelinated sections in between, which speeds up transmission.

Depolarized region (node of Ranvier) Cell body Schwann cell Myelin sheath Axon Depolarized region (node of Ranvier) + + + + + – – – – – Figure 48.15

Synaptic transmission Neurons communicate with other cells at synapses, which are junctions between neurons or between neurons and sensory receptors or muscle cells. The transmitting cell is the presynaptic cell and the receiving cell is the postsynaptic cell.

In an electrical synapse electrical ion currents flows directly from one cell to another via gap junctions. However, the vast majority of synapses are chemical synapses. In a chemical synapse the electrical signal is converted into a chemical signal that travels across the synapse and is converted back into an electrical signal in the postsynaptic cell.

In a chemical synapse, a presynaptic neuron when stimulated by an action potential releases chemical neurotransmitters, which are stored in the synaptic terminal. Figure 48.16 Postsynaptic neuron Synaptic terminal of presynaptic neurons 5 µm

When an action potential reaches a synaptic terminal it depolarizes the membrane and triggers an influx of Ca++ ions. The influx of Ca++ ions causes neurotransmitter molecules to be released into the synaptic cleft.

Voltage-gated Ca2+ channel Figure 48.17 Presynaptic cell Postsynaptic cell Synaptic vesicles containing neurotransmitter Presynaptic membrane Postsynaptic membrane Voltage-gated Ca2+ channel Synaptic cleft Ligand-gated ion channels Na+ K+ Ligand- gated ion channel Neuro- transmitter 1 Ca2+ 2 3 4 5 6

A Chemical Synapse (an example)

Direct Synaptic Transmission The neurotransmitter molecules binds to ligand-gated ion channels and the binding causes the ion channels to open, generating a postsynaptic potential. Neurotransmitter molecules are quickly removed or broken down to terminate the synaptic response. Postsynaptic potentials fall into two categories Excitatory postsynaptic potentials (EPSPs) Inhibitory postsynaptic potentials (IPSPs)

Summation of Postsynaptic Potentials Unlike action potentials postsynaptic potentials are graded because they are influenced by the amount of neurotransmitter released and do not regenerate themselves.

Membrane potential (mV) Since most neurons have many synapses on their dendrites and cell body a single EPSP is usually too small to trigger an action potential in a postsynaptic neuron Figure 48.18a E1 Resting potential Threshold of axon of postsynaptic neuron (a) Subthreshold, no summation Terminal branch of presynaptic neuron Postsynaptic neuron –70 Membrane potential (mV)

If two EPSPs are produced in rapid succession an effect called temporal summation occurs in which the effects added together produce an action potential. E1 Action potential (b) Temporal summation Axon hillock

In spatial summation EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron add together E1 + E2 Action potential (c) Spatial summation E1 E2

Through summation an IPSP can counter the effect of an EPSP Figure 48.18d E1 E1 + I I (d) Spatial summation of EPSP and IPSP

The input from inhibitory and excitatory is integrated in a part of the neuron called the axon hillock. Acting as the neuron’s integrating center the axon hillock weighs the inputs and if they are sufficient to reach the threshold an action potential is generated and travels along the axon. If the threshold is not reached, no action potential is produced.

Neurotransmitters There are a large number of different neurotransmitters and same neurotransmitter can produce different effects in different types of cells.

Table 48.1

Acetylcholine Acetylcholine Is one of the most common neurotransmitters in both vertebrates and invertebrates In the CNS acetylcholine can be inhibitory or excitatory. Acetylcholine is also released at synapses between nerves and muscle cells and induces muscle contraction. Nicotine’s physiological and psychological effects are caused by its binding to acetylcholine receptors

Biogenic Amines Biogenic amines are derived from amino acids and include epinephrine, norepinephrine, dopamine, and serotonin. They are active in both the CNS and PNS. Dopamine and serotonin affect sleep, mood, attention and learning. Parkinson’s Disease is associated with a lack of dopamine production. Prozac enhances the effect of serotonin by slowing its uptake after release.

Amino Acids and Peptides Various amino acids and peptides are active as neurotransmitters in the brain. These include the neuropeptides called endorphins, which act as natural analgesics reducing the perception of pain. Opiates such as heroin and morphine bind to endorphin receptors in the brain.

Concept 48.5: The vertebrate nervous system is regionally specialized In all vertebrates, the nervous system shows a high degree of cephalization and distinct CNS and PNS components Figure 48.19 Central nervous system (CNS) Peripheral nervous system (PNS) Brain Spinal cord Cranial nerves Ganglia outside CNS Spinal

The brain provides the integrative power that underlies the complex behavior of vertebrates The spinal cord integrates simple responses to certain kinds of stimuli and conveys information to and from the brain

The Peripheral Nervous System The PNS transmits information to and from the CNS and plays a large role in regulating a vertebrate’s movement and internal environment

The PNS can be divided into two functional components The somatic nervous system and the autonomic nervous system Peripheral nervous system Somatic nervous system Autonomic Sympathetic division Parasympathetic Enteric Figure 48.21

The somatic nervous system carries signals to skeletal muscles The autonomic nervous system regulates the internal environment, in an involuntary manner The autonomic nervous system is divided into the sympathetic, parasympathetic, and enteric divisions. The sympathetic and parasympathetic divisions have antagonistic effects on target organs.

The sympathetic division correlates with the “fight-or-flight” response: arousal and energy generation. Heart beats faster, bronchi dilate, digestion is inhibited, epinephrine (adrenalin) is released. The parasympathetic division promotes a return to self-maintenance functions. Promotes calming. The enteric division controls the activity of the digestive tract, pancreas, and gallbladder

Parasympathetic division Action on target organs: Location of preganglionic neurons: brainstem and sacral segments of spinal cord Neurotransmitter released by acetylcholine postganglionic neurons: in ganglia close to or within target organs Constricts pupil of eye Stimulates salivary gland secretion Constricts bronchi in lungs Slows heart Stimulates activity of stomach and intestines of pancreas Stimulates gallbladder Promotes emptying of bladder Promotes erection of genitalia Cervical Thoracic Lumbar Synapse Sympathetic ganglia Dilates pupil Inhibits salivary Relaxes bronchi in lungs Accelerates heart Inhibits activity of stomach and intestines Inhibits activity Stimulates glucose release from liver; inhibits gallbladder adrenal medulla Inhibits emptying Promotes ejaculation and vaginal contractions Sacral thoracic and lumbar some in ganglia close to target organs; others in a chain of ganglia near spinal cord norepinephrine Figure 48.22