Lecture 8 Nervous System

Neuroscience

• Neuroscience is the study of the nervous system, focusing on how the brain functions and understands.

Summary of Nervous System

• Key functions:

  • Sensory input: Gathering information from the environment.

  • Integration: Processing and interpreting sensory information.

  • Motor output: Responding to processed information through actions.

Organization of the Nervous System

• CNS (Central Nervous System): Brain and spinal cord.

• PNS (Peripheral Nervous System): Peripheral nerves, ganglia, and sensory receptors.

• Afferent: Sensory pathways.

  • Somatic: Conscious senses.

  • Autonomic: Visceral organs.

• Efferent: Motor pathways.

  • Somatic: Skeletal muscle.

  • Autonomic: Smooth muscle, glands.

• Autonomic:

  • Sympathetic: "Fight or flight" responses.

  • Parasympathetic: "Rest and digest" functions.

Neurons and Glia

• Two cell types in nervous systems:

  • Neurons: Generate and conduct electric signals for communication.

  • Glia:

    • Macroglia: Modulate neuron activity and provide support.

    • Microglia: Immune defense in the nervous system; phagocytic cells.

Glial Cells

• Support neurons physically and biochemically.

• Outnumber neurons 10 to 1.

• CNS: oligodendrocytes, microglia, astrocytes, ependymal cells.

• PNS: Schwann cells, satellite cells.

Astrocytes and the Blood-Brain Barrier

• Astrocytes form the blood-brain barrier, protecting the brain from toxins.

• Other functions:

  • Neurotransmitter uptake from the synapse.

  • Glycogen storage for neuron fuel.

  • Neurotransmitter release to alter neuron activities.

  • Aid in neuron repair and regeneration.

  • Signal changes in blood composition.

• Contact over 100,000 synapses.

• Tripartite synapse: Pre- and postsynaptic neurons with astrocyte connections.

The Glymphatic System

• Interstitial fluid enters the brain via perivascular spaces around arteries and astrocytes.

• Astrocytes use aquaporins to distribute fluid to interstitial spaces.

• Fluid exits via perivascular spaces of veins, removing metabolic waste.

Myelination

• Oligodendrocytes (in the brain and spinal cord) and Schwann cells (other nerves) wrap around axons, forming insulating myelin sheaths.

Origin and Regeneration

• Vertebrates have a CNS (brain and spinal cord) and PNS for communication.

• Neurons and macroglia from neural stem cells in the neural tube.

• Neural stem cells divide into stem cells and neuroblasts/glioblasts.

• Committed neurons typically do not regenerate.

Neuron Structure

• Cell body: Contains nucleus and organelles.

• Dendrites: Receive information.

• Axon: Transmits information.

• Axon terminals: At the tip of the axon.

• Neuron form reflects function; dendrite number indicates information sources; axon length varies with communication distance.

Neuron Function and Electric Potential

• Neurons communicate through changes in electric potential across membranes.

• Action potentials (APs) are rapid, large membrane potential changes.

• Sodium-potassium pumps create Na^+ and K^+ gradients.

• "Leak channels" cause a negative inside charge relative to the outside.

• Membrane potential: Charge difference due to K^+ diffusion and electrical potential.

• Resting Membrane potential: Steady-state membrane potential of a neuron.

Voltage and Electric Current

• Voltage: Force causing charged particle movement.

• Electric current in neurons is carried by ions (Na^+, K^+, Ca^{2+}, Cl^–).

• Resting potential of an axon: -60 to -70 mV.

• Stimuli change membrane permeability, allowing ion movement.

Action Potentials

• Action potentials are sudden reversals in membrane voltage.

• Positively charged ions flow in, making the inside more positive.

• Ion transporters and channels distribute charges.

• The sodium–potassium pump moves Na^+ out and K^+ in, requiring energy.

Ion Channels and Electrochemical Gradient

• Ion channels are selective for specific ions.

• Ion movement depends on concentration gradient and voltage difference (electrochemical gradient).

• Potassium channels open in the resting membrane, and K^+ ions diffuse out.

• Nernst equation calculates E_K from ion concentrations: E*{ion} = 2.3 \frac{RT}{zF} \text{log} \frac{[ion]_o}{[ion]_i}

Patch Clamping

• Studies ion channels by placing an electrode on the membrane to measure ion movement and channel activity.

Gated Ion Channels

• Gated ion channels respond to stimuli:

  • Voltage-gated channels: Respond to voltage changes.

  • Chemically-gated channels: Respond to specific molecules.

  • Mechanically-gated channels: Respond to force.

Depolarization and Hyperpolarization

• Gated channels alter membrane potential.

• Depolarization: Inside becomes less negative due to Na^+ influx.

• Hyperpolarization: Membrane becomes more negative due to K^+ efflux.

Graded Membrane Potentials

• Changes in resting potential proportional to stimulus magnitude; integrate input by summing depolarization or hyperpolarization.

Action Potentials and Voltage-Gated Channels

• Action potentials are large changes in membrane potential, caused by voltage-gated Na^+ and K^+ channels.

• Depolarization at the axon hillock opens Na^+ channels, causing Na^+ influx and more depolarization (positive feedback).

Threshold and Action Potential Generation

• Threshold: Depolarization of 5-10 mV above resting potential triggers an action potential.

• The axon returns to resting potential as Na^+ channels close and K^+ channels open.

• Voltage and ion permeability changes during the action potential:

  1. Membrane depolarizes to threshold.

  2. Voltage-gated Na^+ channels open, and Na^+ enters cell.

  3. Voltage-gated K^+ channels begin to open slowly.

  4. Rapid Na^+ entry depolarizes cell.

  5. Na^+ channels close, and slower K^+ channels open.

  6. K^+ moves from cell to extracellular fluid.

  7. K^+ channels remain open, and additional K^+ leaves cell, hyperpolarizing it.

  8. Voltage-gated K^+ channels close, less K^+ leaks out of the cell.

  9. Cell returns to resting ion permeability and resting membrane potential.

• All or None!

All-or-None Principle and Impulse Intensity

• It is an all-or-none event—positive feedback to voltage-gated Na^+ channels ensures the maximum action potential.

• Either an axon conducts a nerve impulse, or it does not.

• Message intensity is determined by action potential frequency.

Continuous Propagation of Action Potential

• Continuous Propagation of AP along an unmyelinated axon

• Affects one segment of axon at a time

  1. Action potential in segment 1

     • Depolarizes membrane to +30 mV

  2. Local current

  3. Depolarizes second segment to threshold

     • Second segment develops action potential

Refractory Period

• A short period after an impulse during which the axon cannot conduct another impulse, ensuring one-way travel.

  • Voltage-gated K^+ channels contribute to the refractory period by remaining open.

  • Efflux of K^+ ions makes the membrane potential less negative than the resting potential for a brief period.

  • After-hyperpolarization or undershoot: the dip in membrane potential after an action potential.

Action Potential Propagation

• Action potentials travel long distances without signal loss by regenerating at adjacent membrane regions; they cannot reverse due to the refractory period.

Saltatory Conduction

• Action potentials travel faster in myelinated axons.

• Nodes of Ranvier are gaps in the myelin where action potentials are generated.

• Saltatory Propagation: Action potential along myelinated axon

  • Faster and uses less energy than continuous propagation

  • Myelin insulates axon, prevents continuous propagation

  • Local current “jumps” from node to node

  • Depolarization occurs only at nodes

Synapses and Neurotransmission

• Axon terminals form synapses with target cells.

• Action potentials cause neurotransmitter release from the presynaptic cell, which diffuses to receptors on the postsynaptic cell.

• Neurons integrate information by summing excitatory and inhibitory inputs.

Chemical Synapses and the Neuromuscular Junction

• Chemical synapses are common in vertebrates.

• Neuromuscular junctions (NMJ) are synapses between motor neurons and skeletal muscle cells.

• Neurotransmitter: acetylcholine (ACh).

• ACh diffuses across the synaptic cleft to the motor end plate on the muscle cell.

• An action potential causes release of the neurotransmitter ACh when voltage-gated Ca^{2+} channels open and Ca^{2+} enters the axon terminal.

• Vesicles release ACh into the synaptic cleft by exocytosis.

Synaptic Transmission

• ACh binds to receptors (AChRs) on the motor end plate, causing Na^+ influx and membrane depolarization (graded potential).

• Synapses can be excitatory (depolarization) or inhibitory (hyperpolarization).

• Neurons receive diverse chemical messages.

Summation of Postsynaptic Potentials

• Neurons have dendrites that form synapses with other neurons.

• The mix of excitatory and inhibitory activity determines the graded membrane potential.

• Summation of postsynaptic potentials integrates information.

• Each neuron receives many synaptic inputs but has one axon for output.

• Temporal and Spatial Summation.

  • Temporal Summation: Temporal summation occurs on a membrane that receives two depolarizing stimuli from the same source in rapid succession. The effects of the second stimulus are added to those on the first.

    1. First stimulus arrives

    2. Second stimulus arrives and is

    3. Action potential is generated

  • Spatial Summation: Spatial summation occurs when sources of stimulation arrive simultaneously, but at different locations. Local currents spread the depolarizing effects, and areas of overlap experience the combined effects.

    1. Two stimuli arrive simultaneously

    2. Action potential is generated

• Summation occurs in the axon hillock, which has many voltage-gated Na^+ channels.

• Postsynaptic potentials spread to the axon hillock by local current flow.

Spatial and Temporal Summation

• Excitatory and inhibitory postsynaptic potentials are summed over space and time.

• Spatial summation adds messages at different synaptic sites.

• Temporal summation adds potentials at the same site in rapid sequence.

Termination of Neurotransmitter Effects

• Neurotransmitters must be cleared from the synaptic cleft.

• Breakdown by enzymes: ACh is broken down by acetylcholinesterase (AChE); inhibition causes spastic paralysis.

• Neurotransmitters diffuse away or are taken up by glial cells.

• Prozac slows serotonin reuptake, enhancing its activity.

Mechanisms of Neurotransmitter Removal

• Neurotransmitter effect is terminated in one of three ways:

  • Reuptake- By astrocytes or axon terminal

  • Degradation- By enzymes

  • Diffusion- Away from synaptic cleft

Common Neurotransmitters

• Amino acids: Glutamate (excitatory), Glycine and GABA (inhibitory).

• Other neurotransmitters: Acetylcholine, Monoamines (dopamine, norepinephrine, serotonin), Peptides (endorphins, enkephalins, substance P), Nitric oxide.

Neurotransmitter Receptors and Drug Effects

• Neurotransmitters have multiple receptor types with different effects.

• Drugs affect synaptic interactions:

  • Agonists: Mimic or potentiate neurotransmitters.

  • Antagonists: Block neurotransmitters.

  • Morphine is an agonist at the endorphin receptor.

Functions Are Localized in the Nervous System

• Vertebrate nervous systems:

  • Central nervous system (CNS): brain and spinal cord

  • Peripheral nervous system (PNS): nerves that connect the CNS to all tissues and sensors of the body

  • Enteric nervous system: in the gut

  • Nerve: bundle of axons in the PNS that carries information.

  • Tract: bundle of axons in the CNS that carries information.

  • Peripheral nervous system:

    • Afferent nerve carries information from sensory receptor cells to the CNS.

    • Efferent nerve carries information from the CNS to muscles and glands.

    • Both have conscious and unconscious divisions.

Structure and Function of the PNS and CNS

• Central nervous system (CNS)

  • Brain and spinal cord

  • Integrative and control centers

• Peripheral nervous system (PNS)

  • Cranial nerves and spinal nerves

  • Communication lines between the CNS and the rest of the body

  • Sensory (afferent) division

    • Somatic and visceral sensory nerve fibers

    • Conducts impulses from receptors to the CNS

  • Motor (efferent) division

    • Motor nerve fibers

    • Conducts impulses from the CNS to effectors (muscles and glands)

Development of the CNS

• The CNS develops from the neural tube of an embryo.

• The anterior part develops into the hindbrain, midbrain, and forebrain.

• The rest becomes the spinal cord.

• Information flow in the adult nervous system will follow paths that emerge from the linear neural tube.

The Embryonic Nervous System

• The neural tube develops into the CNS

• The neural crest cells develop into the PNS

• The notochord develops into the vertebral column

• The lumen (hollow space) of the neural tube becomes the ventricles

• Forebrain:

  • Cerebrum, diencephalon

• Midbrain:

  • Mesencephalon

• Hindbrain:

  • Medulla, Cerebellum, Pons

Brain Regions and Their Functions

• Midbrain: Integrates sensory information and coordinates motor responses; key for sensory processing and movement.

• Hindbrain: Medulla, pons, and cerebellum.

  • Medulla and pons control physiological functions, such as breathing.

  • Midbrain, medulla, and pons make up the brainstem.

  • All information traveling between the spinal cord and higher brain areas must pass through the brainstem.

  • The cerebellum coordinates muscle activity and maintains balance; essential for motor coordination.
    -The midbrain, hindbrain, and forebrain are super important to understand neural control. They integrate key body functions with higher-order thought and action.

Forebrain

• Forebrain develops into two regions:

  • Diencephalon: thalamus and hypothalamus.

Spinal Cord Functions

• The spinal cord conducts information to and from the brain and carries out integrative functions.

• Integrates information coming from the PNS and issues motor commands (e.g., knee-jerk reflex, a simple circuit).

• Also coordinates more complex behaviors such as the withdrawal reflex.

Brainstem and Cranial Nerves

• The brainstem regulates autonomic functions (involuntary physiological functions) via 12 paired cranial nerves.

• Includes the olfactory, optic, and auditory nerves.

• Cranial nerve X (vagus nerve) goes to the body cavity and communicates with many organs, including heart and gut.

• Major parasympathetic nerve

Telencephalon and Brainstem Nuclei

• Telencephalon (cerebrum): cerebral hemispheres. Outer layer is the cerebral cortex, a thin layer rich in cell bodies.

• Telencephalization: in vertebrate evolution, the telencephalon increases in size and complexity.

• An anatomically distinct group of CNS neurons is a nucleus.

• An anatomically distinct group of PNS neurons is a ganglion.

• Brainstem nuclei are involved in keeping higher brain areas awake or allowing them to sleep.

• The core of the brainstem is called the reticular activating system. Activity in these complicated sensory pathways can promote wakefulness.

• Damage to the brain or spinal cord below the reticular activating system can result in paralysis but leave sleep–wake cycle behavior normal.

• Damage above the level of the reticular activating system can result in coma.

Thalamus, Hypothalamus, and Limbic System

• Core of the forebrain:

  • Thalamus communicates sensory information to the cerebral cortex.

  • Hypothalamus regulates many homeostatic functions.

  • Surrounding the diencephalon are phylogenetically older structures of the telencephalon called the limbic system.

Limbic System

• Limbic system: responsible for instincts, long-term memory formation, drives such as hunger and thirst, sexual behavior, and emotions.

• Amygdala: involved in fear and fear memory.

• Hippocampus: transfers short-term memory to long-term memory.

Memory Storage

• Storage and retrieval of information

  • Hippocampus and surrounding temporal lobes function in consolidation and access to memory

  • ACh from basal forebrain is necessary for memory formation and retrieval

  • Two stages of storage

    • Short-term memory (STM, or working memory)—temporary holding of information; limited to seven or eight pieces of information

    • Long-term memory (LTM) has limitless capacity

Cerebral Cortex

• The cerebral cortex has a large surface area; it is folded into ridges (gyri) and valleys (sulci).

• These foldings, or convolutions, allow the large surface of the cortex to fit in the skull.

• Left hemisphere mostly controls the right side of the body; right hemisphere controls the left side, except in the head.

• The two hemispheres are not symmetrical with respect to all functions; for example, language abilities reside in the left hemisphere.

Hemispheric Lateralization

• Left Cerebral Hemisphere:

  • Prefrontal cortex

  • Speech center

  • LEFT HAND

  • Writing

  • Auditory cortex (right ear)

  • Visual cortex (right visual field)

  • General interpretive center (language and mathematical calculation)

• Right Cerebral Hemisphere

  • Prefrontal cortex

  • RIGHT HAND

  • Auditory cortex (left ear)

  • Visual cortex (left visual field)

  • Spatial visualization and analysis

  • Analysis by touch

Association Cortex

• Different regions of the cerebral cortex have specific functions.

• Association cortex: areas that integrate or associate sensory information or memories; higher-order information processing.

Temporal Lobe

• Receives and processes auditory information

• Association areas involve identifying and naming objects

• Agnosias: inability to identify objects.

• Damage in certain areas causes inability to recognize faces or understand spoken language.

Frontal Lobe

• Central sulcus divides frontal and parietal lobes.

• Primary motor cortex is in front of the central sulcus; controls muscles in specific body areas.

• Parts of the body with fine motor control, such as face and hands, have disproportionate representation.

Frontal Lobe Association Areas

• Association areas of the frontal lobe have to do with feeling and planning.

• They are said to have executive function and contribute significantly to personality.

• People with frontal lobe damage can have drastic changes in personality.

Parietal Lobe

• Primary somatosensory cortex is just behind the central sulcus.

• Receives touch and pressure information from the thalamus

• The entire body surface can be mapped; areas with high densities of mechanoreceptors have disproportionate representation.

• Association functions: attending to complex stimuli.

• Damage to right parietal lobe causes contralateral neglect syndrome: person is unable to recognize stimuli from left side of body.

• Damage to the left parietal cortex does not cause the same degree of neglect of the right side of the body.

Occipital Lobe

• Receives and processes visual information

• Association areas involve:

  • Making sense of the visual world

  • Translating visual experience into language

Insular Cortex

• Receives a great variety of afferent information

• Appears to integrate physiological information from all over the body to create a sensation of how the body “feels”

Evolution of the Human Brain

• In vertebrates, body size and brain size are correlated, but higher primates fall above this regression line.

• In humans, the cerebral cortex is the largest brain area and is made even larger by convolutions.

• The percent of cortex devoted to integration of information (association cortex) is greatest in humans.

Nervous System Complexity

• Nervous systems vary in complexity.

• Cnidarians have simple nerve nets. There is little or no integration or processing of signals.

• More complex animals must process and integrate larger amounts of information. Neurons are organized into clusters called ganglia.

• In bilaterally symmetrical animals, ganglia are often paired; they may be enlarged and fused at the anterior end to form a brain.

• Most cells of vertebrate nervous systems are in the central nervous system.

• Sensory and effector neurons and their supporting cells are the peripheral nervous system.

Spinal Reflexes

• The knee-jerk reflex is an autonomic spinal reflex involving neurons that connect in the spinal cord.

• Gray matter is rich in neural cell bodies; white matter contains myelinated axons.

• Afferent (sensory) axons in a spinal nerve enter the spinal cord through the dorsal root; efferent (motor) axons leave through the ventral root.

• Most spinal networks are more complex.

• Limb movements are coordinated by antagonistic sets of muscles—flexors and extensors.

• This coordination is achieved by an interneuron between the sensory neuron and the motor neuron of the antagonist muscle.

Autonomic Nervous System (ANS)

• Includes CNS and PNS components

• Controls involuntary functions *Involuntary- Smooth, cardiac muscle; glands

  • Multiple efferent neurons

  • Axon terminals release acetylcholine or norepinephrine

  • Can be excitatory or inhibitory

  • Controlled by the homeostatic centers in the brain – pons, hypothalamus, medulla oblongata

Cholinergic Neurons and Ganglia

• All autonomic efferent pathways begin with preganglionic cholinergic neurons; cell bodies are in the brainstem or spinal cord, axons connect to a ganglion outside the CNS.

• Postganglionic neuron cell bodies are in the ganglia, the axons synapse with cells in target organs.

Antagonistic Control in the ANS

• Most internal organs are under antagonistic control

• One autonomic branch is excitatory, and the other branch is inhibitory

• Example:

  • Effector organ: heart

  • Parasympathetic response: slows rate

  • Sympathetic response: increases rate and force of contraction

Sensory Receptor Cells

• Sensory receptor cells (sensors or receptors) transduce physical and chemical stimuli into neural signals.

• Sensory transduction begins with a receptor protein that opens or closes ion channels in the membrane, changing the membrane potential (receptor potential).

• Receptor potentials are graded membrane potentials that travel a short distance.

• The receptor potential must generate action potentials in the receptor cell.

• Or release neurotransmitters that can start action potentials in a postsynaptic cell.

Receptor Potentials and Photosensitivity

• Some receptor cells don’t fire action potentials.

• The receptor potential reaches a presynaptic patch of cell membrane and induces release of a neurotransmitter.

• Intensity of the stimulus influences how much neurotransmitter is released.

• Photosensitivity: sensitivity to light.

• A range of animal species from simple to complex can sense and respond to light.

• The molecular basis for photosensitivity is a family of visual pigments that have been evolutionarily conserved.

• Pigments are in photoreceptor cells that transform light energy into action potentials.

Invertebrate Visual Systems

• Invertebrate visual systems range from simple to complex.

• Flatworms have photoreceptor cells in paired eye cups that give directional information.

• Photoreceptors on the two sides are unequally stimulated unless the animal is facing directly toward or away from a light source.

• Arthropods have compound eyes consisting of many optical units called ommatidia.

• Each ommatidium has a narrow-angle lens to focus light onto photoreceptor cells; directed at a slightly different part of the visual world.

• Only a low-resolution (pixelated) image can be communicated to the CNS.

Vertebrate and Cephalopod Eyes

• Vertebrates and cephalopod mollusk eyes consist of one optical unit with a wide-angle lens that can form detailed images of the visual world.

• Like cameras, they focus inverted images on a surface that is sensitive to light.

• They evolved completely independently of each other, but their degree of similarity is remarkable.

The Vertebrate Eye

• Vertebrate eye is surrounded by sclera (tough connective tissue), which becomes the transparent cornea on front of eye.

  • Iris—controls amount of light reaching photoreceptors; pigmented; opening is the pupil.

  • In bright light, the iris constricts and pupil is small; in dim light, iris relaxes and pupil is large.

  • Lens—crystalline protein; focuses image on the retina.

  • In birds and mammals, the lens changes shape. Ciliary muscles contract, rounding the lens to focus on near objects. When the muscle relaxes, the lens is flattened, to focus on far objects.

    • Fishes, amphibians, and reptiles focus by moving the lens closer to or farther from the retina.

Retina and Opsin

• Retina: five layers of cells that light must pass through.

• In humans, light not captured is absorbed by a pigmented layer.

• Nocturnal animals have an iridescent reflective layer behind their retinas, which maximizes capture of photons by reflecting them back onto the photoreceptors.

• Opsins: photoreceptor molecules in animals are proteins with functional groups called 11-cis-retinal.

• Retinal absorbs photons of light; color of the light received depends on structure of the opsin.

• Rhodopsin is the most common opsin; gives humans sensitivity to low levels of light, but not color.

• When 11-cis-retinal absorbs photons of light it changes to the isomer all-trans-retinal, which changes the conformation of opsin.

• This triggers a cascade of reactions involving G protein signaling and results in alteration of membrane potential of the photoreceptor cell.

Rod and Cone Cells

• Photoreceptors: modified neurons

  • Rod cells: highly light-sensitive and perceive shades of gray in dim light.

  • Cone cells: function at high light levels; responsible for high-acuity color vision.

Distribution of Rods and Cones

• Cone cells are concentrated in the center of the visual field, the fovea.

• They have low sensitivity to light and contribute little to night vision.

• Rod cells are more on the peripheral of the retina; they are more low light sensitive and contribute mostly to night vision and movements.

• Nocturnal animals’ retinas have a high percentage of rod cells; day-active animals have more cone cells.

Human Cone Cells and Color Vision

• Humans have three types of cone cells with slightly different opsin molecules that absorb different wavelengths of light.

• This allows the brain to interpret input from the different cones as a full range of color.

• Color blindness is the loss of function of one or more types of cone cells.

Neurons in the Retina

• The retina has five types of neurons arranged in layers.

• Rods and cones are at the back.

• Axons from ganglion cells at the front of the retina form the optic nerve and send input to the brain.

• A central layer contains bipolar cells, horizontal cells, and amacrine cells.

Photoreceptor Connections

• Photoreceptor cells are connected to ganglion cells via bipolar cells.

• Changes in photoreceptor membrane potential in response to light alter their neurotransmitter release onto bipolar cells.

• Rate of neurotransmitter release from bipolar cells determines the rate at which ganglion cells fire action potentials.

• A ganglion cell gets input from several photoreceptors; as few as five in the fovea; up to thousands in the periphery.

• A patch of photoreceptors forms a circular receptive field. Light may excite or inhibit the ganglion cell, thus giving information about the pattern of light and dark falling on the retina.

• Horizontal and amacrine cells communicate laterally across the retina; they sharpen contrast and adjust the sensitivity of the retina