OBI 814 - Estus Lecture 1 - Exam 2

• The brain accounts for 2% of body mass, yet consumes 20% of resting body energy

Nervous System Overview

• The CNS consists of the brain and spinal cord
  • It maintains internal homeostasis
  • It receives sensory input and plans responses
• The PNS consists of axons and autonomic neuron ganglia (cell bodies) outside the brain and cord
  • Relays sensory information to the CNS
  • Executes brain plans

CNS Structure and Function

• Cerebrum includes multiple lobes and is responsible for conscious perceptions, thought, and action
• Cerebellum (minibrain) balances and modulates complex movement

Human Brain Structure Function

• Assessment of challenges involves multiple brain structures
  • The visual system identifies ball, size, direction, and velocity
  • The amygdala coordinates sensory response with emotion/motivation
  • The hypothalamus regulates homeostatic functions like heart rate and respiration

Visual System

• The visual system detects incoming photons to generate images of space
• Rods and cones in the retina detect photons, relaying the signal to the visual cortex
• "Simple" cortical neurons in the visual cortex, detect convergent rod and cone signals as line segments
• Multiple simple cells signal "complex" cortical neurons to integrate their signal and detect line segment movement
• The frontal lobe analyzes this signal for trajectory and timing
• Vision is a learned sense where light stimulation points are converted into line segments and movement

Neural Coordination

• Premotor cortex plans motor and signals to the motor cortex
• Motor cortex signals spinal cord to constrict muscles
• Basal Ganglia initiates motor patterns
• Cerebellum fine tunes with proprioceptive information from peripherals sensors
• Posterior parietal lobe defines location in 3D space for body and limbs
• Hippocampus forms memory of the event

Amygdala Function

• The amygdala (almond-shaped) stimulates multiple CNS areas
• Links sensory input to emotional or motivational responses
• The hypothalamus receives part of the amygdala's output

Hypothalamus Function

• The hypothalamus receives input from many areas including the amygdala
• The hypothalamus output integrates behavior and homeostatic regulation (autonomic nervous system)

Premotor Cortex

• The premotor cortex plans complex movements
• A complex sequence of movements increases blood flow in an additional premotor region
• Mental rehearsal increases blood flow only in the premotor cortex

Motor Pathway

• Neurons in the motor cortex send axons down the corticospinal tract
  • This modulates motor neurons that control muscle movements
  • The corticospinal tract is a large bundle fiber with 1 million axons
• Motor cortex neurons then release glutamate onto motor neurons, activating them
• Tracts named in “from here to there" fashion
  • Corticospinal - from the cortex to the spine
  • Spinothalamic - from the spine to the thalamus
• Note that the brain hemisphere controls contralateral muscle

Motor Homunculus

• Neuron neighbors in the motor cortex control neighboring muscles in the periphery
• Motor and somatosensory cortices are adjacent on the surface of the brain

Motor Control Overview Model

• The higher centers (command neurons) control intention, motivation, memory, and emotion
• Sensorimotor lumps are pre-motor, motor, and somatosensory cortex
• Middle Level integrates afferent sensory information (body parts and environment) with command information to execute a ‘motor program’
• Local Level- motor neurons in the brainstem and spinal cord that send axons from the CNS to innervate muscles
• Constant feedback adjusts the motor program so actual movements approach desired movements

Basal Ganglion

• The basal ganglia initiates motor movements based on sensory and motor feedback
• Influences initiation but does not direct movements, without directs connections to with the spinal cord
  • Parkinson's Disease demonstrates diminished initiation
  • Huntington's Disease demonstrates excessive movement

Cerebellum

• The Cerebellum (little brain)
• Regulates (coordinating) balance and posture, voluntary movements, and motor learning
• Corrects for errors between actual and intended actions while the movement is in progress
• Sends output to the brainstem and the cerebral cortex
• Receives sensory information (tactile and proprioceptive) from the body

Posterior Parietal Cortex

• The posterior parietal cortex integrates proprioception, overall somatic (body) sensory information with other modalities (vision and hearing)
• Creates a 3D model of the environment relative to our bodies
• Damage demonstrates the patient is unable to replicate the contralateral portion of models

Cortical Integration (motor plan)

• The premotor cortex is the main controller for motor planning/integration
• Pools sensory information (visual, auditory, vestibular, somatosensory); involved in visual control of reaching and grasping
• Brainstem -> Spinal cord ->cerebellum

Working and Long-Term Memory

• Sensory inputs enter your sensory memory but last less than a second
• Action/Attention on the information moves it to working memory
• Retrieval of existing knowledge and work associate with new information leading to encoding new memories
• The encoding of memories, stores material in long-term memory

Memory Types

• Within long term memory
  • Explicit (declarative) memories are those such as facts and events
  • Implicit (nondeclarative) memories are those such as priming, procedural skills and habits, classical/operant conditioning, and habituation/sensitization reflexes
• The medial temporal lobe includes the hippocampus
  • Patients with hippocampus resection have lost the ability to consolidate short term memories

Hippocampal-Cortical Connections

• Critical to memory formation and storage
• Permanent memory storage requires strengthening of synapses between the hippocampus and areas of the cortex
• Electroconvulsive therapy (ECT) has caused patients with severe depression to have transient damage to neocortical areas
  • This causes retrograde amnesia
  • Memories up to 1-3 years prior to ECT can be lost for weeks to months

Types of Neural Cells

• Neurons:
  • Transmit electrical and chemical signals
• Astrocytes:
  • Provide structural support and maintain the extracellular environment of the brain
• Microglia:
  • Immune cells of the brain
• Oligodendrocytes (CNS):
  • Form myelin sheaths around axons in the central nervous system
• Schwann cells (PNS):
  • Form myelin sheaths around axons in the peripheral nervous system
• Ependymal cells:
  • Line the ventricles of the brain and produce cerebrospinal fluid

Neuron Structure

• The cell body (soma) houses the nucleus/RNA that control most protein biosynthesis
• Dendrites integrate information
• Axons propagate action potentials, transport biosynthetics from soma to synapse, transport target-derived proteins back to soma
• Synapses release neurotransmitters onto target cells
  • Excitatory neurotransmitter: acetylcholine, glutamate, adrenergics (Epinephrine/Norepinephrine/Dopamine)
  • Inhibitory neurotransmitter: GABA

Neuron Classification

• Dorsal root ganglion neurons are used by the somatosensory system
• MAP2 is a prototypic dendritic protein
• Tau is a prototypic axonal protein -Synaptophysin is a prototypic synaptic protein
• Neurons are classified by the direction of the signal
  • Afferent - Arrive at the CNS
  • Efferent – Exit the CNS
  • Interneurons – typically small for inter-neuron communication.
• Interneurons account for >99% of all neurons
• Axon : Cell Body ratio =30,000 for a motor neuron

Axonal Transport

• Organelles (mitochondria, endosomes) and large molecules synthesized are too large to diffuse to the synapse
• "Rapid" transport is needed to move resources from the cell body to the synapse
• Cargo gets transported along microtubules via motor proteins that burn ATP
  • Microtubules run the length of the axon (bidirectional "tracks")
  • Kinesins transport proteins/vesicles from the cell body to axon terminals (anterograde transport)
  • Dyneins transport recycled vesicles and proteins from terminals to the cell body (retrograde transport) -Fast axonal transport: vesicular cargo moves ~200–400 mm/day
• Slow axonal transport: cytosolic proteins move 0.2–8 mm/day
• Fast axonal transport: moves a mitochondrion (≈meter length) in ≈hours

Astrocytes

• Astrocytes (star shaped)
  • Serve and protect neurons while maintaining proper cell milieu
• Protect by uptake of residual signaling molecules (glutamate)
• Remove excess glutamate that leads to neuronal overstimulation termed "Excitotoxicity"
• Astrocytes are critical component of the blood-brain barrier

Brain Vascularization

• The cell body lies 10-20 µm from the nearest capillary
• Neurons are high energy dependent, requiring ready access to glucose and oxygen
  • Also require protection from transient neurotoxic agents from the blood stream

Blood Brain Barrier

• Protects the brain from exposure to neurotoxic substances
• Astrocytic end-feet ensheath much of brain vasculature
  • Contain specific transporters for eliminating penetrative molecules
• Blood vessel endothelial cells are connected by tight junctions
  • Pericytes contribute to BBB function
• Tight junctions that prevent free movement of ions
• Lipophilic molecules diffuse/ pass through the membranes.
• Hydrophilic (water soluble) molecules require transporters
• Transport of ATP-binding cassette (ABC) gene family controls influx/efflux chemicals, contributing to challenges treating brain disease
• Increase in glutamate affects calcium levels, causing vasodilation

Oligodendrocytes

• Oligodendrocytes help axon electrical conductance by wrapping axons with myelin
  • Myelin insulates neuronal axons and is produced by oligodendrocytes within the CNS, and Schwann cells within the PNS
  • Wraps axons between nodes of Ranvier, with up to 200 layers of myelin wrapping
  • Myelination increases rate of conduction down the axon by limiting the times it must regenerate electrical potential (Saltatory Conduction)
  • Oligodendrocytes can wrap multiple axons
  • Schwann cells wrap only one axon

Microglia

• Microglia is a cleanup source that resident professional phagocytes of the nervous system
• Prunes unused synapses, digests dying neurons, removes microbes and foreign pathogens
• Regulates inflammatory milieu through release of cytokines
• Activation of these Tightly controlled microglia - overactivity is pathologic, by excessively inflaming and killing viable but damaged neurons
• Microglia act are critical immune brain cells

Ependymal Cells

• Ependymal cells line cerebral ventricles and a subset form the choroid plexus
• The cells are multi-ciliated to move CSF

CSF Factors

• CSF is generated by the choroid plexus
  • Provides physical protection for the brain as well as conduit for removing waste
• It consists of 125-150 ml of filtered plasma + proteins
• Is generated by the choroid plexus at a rate sufficient to replace all CSF every 8 hours
• Exits via arachnoid granulations (one way valves) and lymphatics
• Higher water content than serum (99% vs 93% serum)
• CSF has significantly less protein than Serum(35 vs 7000 mg/dL)
• Slightly higher PH than Serum (7.33 versus 7.41), as well as slight differences in Glucose, Sodium, Potassium, Calcium, Magnesium, and Chloride

Explore the central and peripheral nervous systems, their structures, and functions. Learn about the roles of the cerebrum, cerebellum, and visual system in processing sensory information and coordinating responses. Understand how structures like the amygdala and hypothalamus contribute to complex functions.