OBI 814 Part 2

Brain Regions and Function in Tennis

• The posterior parietal cortex processes visual-spatial information about the ball's trajectory and location to help determine where the ball is going
• The premotor cortex plans motor responses based on the ball's predicted trajectory to help select the proper swing technique
• The basal ganglia initiates the selected motor program and helps coordinate movement sequencing
• The motor cortex sends specific commands to execute the needed muscles for the tennis swing
• The cerebellum coordinates timing and fine-tuning, making adjustments for accuracy and smoothness
• Hippocampus damage would likely cause difficulties in learning/remembering new tennis strategies/techniques, recognizing encountered playing situations, spatial memory of court positioning/tactical patterns, and episodic memory of previous matches regarding what worked/didn't
• Basic motor skills would remain intact, but contextual learning and adaptation are impaired after hippocampus damage
• The amygdala processes the emotional significance of losing, generating feelings of frustration or disappointment
• The amygdala sends signals to the hypothalamus, which activates sympathetic nervous system responses (increased heart rate, blood pressure) and triggers hormonal changes via the HPA axis (cortisol release)
• Hypothalamus activation coordinates physiological aspects of emotional expression (facial expressions, body language), creating the "fight or flight" stress response related to competitive loss
• Astrocytes provide metabolic support to neurons, regulate synaptic transmission and neurotransmitter recycling, maintain ion balance and extracellular homeostasis, form part of the blood-brain barrier, guide neuronal development and synaptogenesis, and participate in inflammatory responses
• Oligodendrocytes form myelin sheaths around axons in the CNS, increase action potential conduction velocity, provide trophic support to axons, enable saltatory conduction, and contribute to axonal integrity and survival
• Newly synthesized proteins are transported from the cell body to the synapse through axonal transport
• Fast axonal transport occurs at 100-400 mm/day for vesicles and mitochondria
• Slow axonal transport occurs at 1-5 mm/day for cytoskeletal proteins
• Proteins may take minutes to days to reach distant synapses depending on axon length
• Transport is mediated by motor proteins (kinesin for anterograde, dynein for retrograde) along microtubule tracks
• CSF is completely replaced approximately 3-4 times per day, which equates to roughly every 6-8 hours
• Impaired CSF replacement can lead to accumulation of metabolic waste products, altered brain homeostasis, increased intracranial pressure, hydrocephalus, impaired nutrient delivery, and potential neurotoxicity/neuroinflammation
• Challenging chemical properties for crossing the blood-brain barrier include high molecular weight (>400-500 Da), high polarity/hydrophilicity, multiple hydrogen bond donors/acceptors, and ionized/charged molecules at physiological pH
• Molecules requiring specialized transporters to cross the blood-brain barrier include glucose (via GLUT1), amino acids, nucleosides, vitamins (B vitamins, vitamin C), hormones (thyroid hormones), large peptides and proteins, and ions (Na+, K+, Ca2+)

Membrane Potentials and Action Potentials

• The Na+/K+ ATPase actively transports 3 Na+ ions out of the cell while bringing 2 K+ ions into the cell to create an electrochemical gradient
• These processes create and maintain concentration gradients, resulting in high Na+ concentration outside and high K+ concentration inside the cell
• The pump is electrogenic and moves more positive charge out than in, directly contributing about -10mV to the resting potential.
• Ion gradients combined with differential membrane permeability establish the resting membrane potential of approximately -70mV
• Increased extracellular K+ depolarizes the resting membrane potential (less negative) as the K+ equilibrium potential shifts
• The threshold for action potential generation remains relatively constant, but neurons become more excitable because the membrane is closer to the threshold
• Action potential amplitude decreases because the driving force for K+ efflux during repolarization is reduced
• Resting state involves minimal ion movement and slight leakage of K+ out of the cell
• The depolarization phase occurs as Na+ channels open, causing Na+ to rapidly move into the cell
• Peak: Na+ channels begin inactivating, Na+ influx slows
• The repolarization phase occurs as K+ channels open and K+ rapidly moves out of the cell
• Hyperpolarization (undershoot) occurs as K+ channels remain open longer than needed, causing excessive K+ to move out of the cell
• Return to resting: K+ channels close, Na+/K+ pump restores ion gradients
• Lidocaine functions as a local anesthetic by blocking voltage-gated sodium channels
• Lidocaine binds to the intracellular portion of Na+ channels when they are open or inactivated
• Lidocaine prevents the channels from returning to the resting state and being available for activation
• Without functional Na+ channels, neurons cannot generate action potentials
• Pain-transmitting neurons (nociceptors) are particularly sensitive because lidocaine preferentially affects smaller diameter, unmyelinated fibers
• By blocking action potential generation and propagation in sensory neurons, pain signals cannot reach the CNS

Axon Diameter and Myelination

• Larger axon diameter results in faster conduction that is proportional to the square root of the diameter
• Larger diameter axons require more energy usage due to larger membrane surface area with more ion channels, resulting in continuous conduction
• Myelination creates saltatory conduction that jumps from node to node and dramatically increases speed by up to 100x
• Myelination is more energy efficient as the action potentials only occur at nodes of Ranvier and conserves ATP by restricting ion exchange to small areas
• Myelination is more energy efficient because it restricts ion exchange to the nodes of Ranvier (about 1% of the axonal surface), dramatically reducing the ATP needed for ion pumping while achieving faster speeds than would be possible with increased diameter alone
• During an action potential, voltage-gated Na+ channels open but quickly enter an inactivated state
• Na+ channel inactivation occurs when the inactivation gate (h-gate) closes, blocking the channel pore
• Na+ channels cannot reopen until the membrane repolarizes to a negative potential and the inactivation gates reset by removing the "ball and chain" blocking the channel
• This process takes a finite amount of time, roughly 1-2 ms
• No stimulus, regardless of strength, can generate another action potential during the absolute refractory period because Na+ channels are unavailable

Multiple Sclerosis Effects

• Action potential conduction velocity is significantly decreased due to loss of saltatory conduction in multiple sclerosis
• Energy requirements are dramatically increased as continuous conduction requires more Na+/K+ pump activity across the entire axon rather than just at nodes in multiple sclerosis
• Reliability of signal transmission is decreased in multiple sclerosis due to increased probability of conduction failure, temporal dispersion of signals, vulnerability to frequency-dependent conduction block, and increased refractory periods
• These changes lead to the classic symptoms of fatigue, weakness, and sensory disturbances in multiple sclerosis

Motor and Autonomic Nervous Systems

• The motor system is under voluntary conscious control, while the autonomic system operates largely unconsciously
• The motor system uses a single neuron to communicate from the CNS to effector, while the autonomic system uses a two-neuron chain consisting of preganglionic and postganglionic neurons
• The motor system only innervates skeletal muscle, while the autonomic system innervates cardiac muscle, smooth muscle and glands
• Tapping the patellar tendon stretches the quadriceps muscle
• Muscle spindles within the quadriceps detect the stretch
• la afferent sensory neurons carry the signal to the spinal cord
• In the ventral horn of the spinal cord, the afferents directly synapse onto alpha motor neurons
• Alpha motor neurons send signals back to the quadriceps, causing contraction
• The reflex is considered monosynaptic because of one synapse in the circuit, making it the fastest type of reflex
• When the quadriceps contracts forcefully, Golgi tendon organs detect the increased tension
• lb afferent sensory neurons carry the signal to the spinal cord
• These afferents synapse onto inhibitory interneurons in the spinal cord
• The inhibitory interneurons then synapse onto and inhibit alpha motor neurons to the same muscle
• This causes muscle relaxation, which prevents excessive tension that could damage the muscle or tendon
• It acts as a protective mechanism to prevent muscle or tendon damage from excessive force generation

Sympathetic vs. Parasympathetic Comparison

• Sympathetic and parasympathetic preganglionic neurotransmitter: Acetylcholine
• Sympathetic postganglionic neurotransmitter: Norepinephrine
• Parasympathetic postganglionic neurotransmitter: Acetylcholine
• Sympathetic primary receptor types: α1, α2, β1, β2 adrenergic
• Parasympathetic primary receptor types: Muscarinic (M1-M5)
• Sympathetic: Increase heart rate
• Parasympathetic: Decreased heart rate
• Sympathetic: Dilates bronchioles
• Parasympathetic: Constricts bronchioles
• Sympathetic: Decreased motility and secretion in digestive tract
• Parasympathetic: Increased motility and secretion in digestive tract
• Sympathetic: Dilation of the pupil
• Parasympathetic: Constriction of the pupil

Blood Flow

• Blood flow increased to skeletal muscles; working muscles can receive up to 20x normal flow, cardiac muscle, skin and respiratory muscles
• Blood flow decreased to the digestive tract (splanchnic circulation), kidneys and non working muscles
• Sympathetic activation causes vasoconstriction in non-essential vascular beds via α1-adrenergic receptors
• In working muscles, metabolic factors override sympathetic vasoconstriction
• Local metabolites cause vasodilation in active tissues
• Sympathetic cholinergic fibers cause vasodilation in the skin for heat dissipation
• Redness and swelling in painful skin injury from neurogenic inflammation
• Activation of a nociceptive (pain) neuron by a painful stimulus causes action potentials to travel orthodromically towards the CNS to signal pain and antidromically down other neuron branches
• Antidromic signaling causes the release of the inflammatory neuropeptides substance P and CGRP from peripheral nerve endings
• These neuropeptides cause vasodilation and increased vascular permeability
• Increased vascular permeability is caused by mast cell degranulation for further inflammation
• The increased vascular permeability represents an antidromic action, as the signal travels in the direction opposite to the normal sensory pathway

Baroreceptor Reflex

• When standing, blood pools in the lower extremities, reducing venous return and decreasing blood pressure
• Decreased stretch of arterial walls causes decreased firing frequency of baroreceptor neurons
• Sympathetic neurons increase firing frequency to increase heart rate and contractility, cause peripheral vasoconstriction, and increase venous tone
• Parasympathetic neurons decrease firing frequency to reduce vagal inhibition of the heart and allow heart rate to increase; these coordinated changes help restore blood pressure by increasing cardiac output and peripheral resistance

Vasovagal Syncope and Autonomic Dysreflexia

• Vasovagal syncope mechanisms: Triggered by emotional stress, pain, or sight of blood; consists of brief sympathetic activation, a paradoxical reflex involving massive parasympathetic/vagal activation, and sympathetic withdrawal
• These processes cause severe bradycardia, vasodilation, hypotension, and a decreased cerebral blood flow, which can result in loss of consciousness
• The evolutionary basis of vasovagal syncope may be a "playing dead" response or a mechanism to increase cerebral blood flow when supine
• Autonomic dysreflexia in spinal cord injury: A triggering mechanism involves a noxious stimulus below the level of the injury that can be bowel impaction or skin pressure
• Activation of sensory signals enters the spinal cord and activate the sympathetic neurons
• Autonomic dysreflexia in spinal cord injury: Normal inhibitory signals from brain centers cannot descend past the injury, resulting in uncontrolled sympathetic activation below the level of injury
• Paradoxical cardiovascular responses consisting of severe hypertension from widespread vasoconstriction below the injury, baroreceptors detect this hypertension and signal the brain
• In paradoxical cardiovascular responses, the the brain attempts to decrease blood pressure by increasing parasympathetic activity, but this causes bradycardia despite the hypertension and Vasodilation occurs only above the level of injury, vasoconstriction persists below the injury level
• Autonomic dysreflexia is a medical emergency because the extreme hypertension can cause stroke, seizures, or retinal hemorrhage, blood pressure can reach dangerously high levels, and the patient cannot regulate the response due to the spinal cord disconnection

Sensory Systems

• Sensory systems: Encoding stimulus intensity through Action potential frequency of individual sensory neurons (first-order)
• Action potential frequency: Stronger stimuli generate higher firing rates
• Threshold differences: Different neurons begin responding at different stimulus intensities
• Adaptation rates: Some neurons respond transiently, others maintain response
• Receptor potential magnitude: Larger receptor potentials with stronger stimuli
• Population coding across multiple neurons
• Recruitment: Stronger stimuli activate more neurons
• Range fractionation: Different neurons respond optimally to different intensity ranges (spatial summation)
• Labeled lines: Specific pathways for different modalities maintain intensity information
• Lateral inhibition: Enhances contrast between different intensity levels

Discrimination

• In two-point discrimination, two points can be identified as separate when they activate different receptive fields with non-overlapping cortical representations
• This reveals smaller receptive fields which all offer better discrimination
• Smaller receptive fields: Fingertips ~2-4mm, back ~40-50mm
• Cortical representation: Body regions with better discrimination have disproportionately larger cortical areas in the somatosensory cortex, cortical magnification
• Areas with high tactile acuity have smaller receptive fields and larger cortical representation
• Areas with low acuity have larger receptive fields and smaller cortical representation
• Lateral inhibition occurs when an activated sensory neuron inhibits its neighbouring neurons
• This creates enhanced contrast at boundaries between stimuli
• Example: When a bright edge appears next to a darker area, the photoreceptors seeing the bright area inhibit adjacent receptors, making the darker area appear even darker at the boundary
• The benefits of example: Enhanced edge detection, Improved spatial discrimination between nearby stimuli, Increased contrast sensitivity, More precise localization of stimuli and Better feature extraction from complex sensory scenes

Sensory Adaptation

• Function sensory adaptation: Rapid adaptation and slow adaptation
• Rapid adaptation (phasic receptors): Respond primarily to stimulus onset/offset or changes
• Examples of rapid adaption: Pacinian corpuscles, hair follicle receptors
• Function: Rapid Adaptation detects motion, vibration, changes in stimuli
• Significance: Helps with environmental and prevents sensory overload
• Slow adaptation (tonic receptors): Maintain response during continued stimulation
• Examples of slow adaptation: Merkel cells, Ruffini endings
• Functions: Provide ongoing information about sustained stimuli
• Significance: Helps with proprioception, posture, continuous pressure
• Central adaptation: Occurs at CNS level rather than receptor level
• EX: Olfactory adaptation in olfactory bulb
• Function: Filters out background or irrelevant stimuli
• Allows focus on novel or changing stimuli
• Fast adaptation: Beneficial for detecting predators, prey, or environmental changes
• Slow adaptation: Necessary for maintaining posture, grip, and awareness of body position

TRP Channels

• The TRP channels response to capsaicin and menthol
• Capsaicin (hot peppers): Activates TRPV1 channels
• TRPV1 is normally activated by temperatures >43°C
• Capsaicin binding causes the channel to open at normal body temperature
• This allows cation influx, generating action potentials in nociceptive neurons
• The brain interprets this as a heat/burning sensation
• Menthol: Activates TRPM8 channels (Transient Receptor Potential Melastatin 8)
• TRPM8 is normally activated by temperatures <26°C
• Menthol binding causes the channel to open at normal body temperature
• Generates action potentials in cold-sensitive neurons
• The brain interprets this as a cooling sensation

Peripheral Sensitization

• The molecular mechanisms of the peripheral sensitization
• Inflammatory mediators are released from damaged tissue
• Mediators: Prostaglandins, bradykinin, serotonin, NGF
• These bind to receptors on nociceptor endings
• Activates intracellular signaling cascades
• PKA, PKC
• Pathways phosphorylate ion channels
• TRPV1, Nav1.8
• Phosphorylation increases channel sensitivity and expression
• Changes in pain threshold
• Lower threshold for activation
• Normally non-painful stimuli become painful
• Increased response to painful stimuli
• Spontaneous activity of nociceptors without stimulus
• Expanded receptive fields
• Protects injured tissue from further damage
• Encourages behaviors that minimize reinjury during healing
• Medial lemniscus vs. lateral spinothalamic pathways
• Lateral spinothalamic pathways consist touch, vibration, proprioception, pressure and medial lemniscus includes Pain, temperature, crude touch

Nerve Signal Speed

• Lateral spinothalamic: Fast (heavily myelinated)
• Medial lemniscus: Slower : (less myelinated)
• Number of synapse consist medail lemniscus and lateral spinothalamic
• Medial lemniscus: Three (1st in dorsal root ganglion, 2nd in medulla, 3rd in thalamus)
• Lateral spinothalamic:Three (1st in dorsal root ganglion, 2nd in spinal cord, 3rd in thalamus)
• Anatomy pathways: Medial lemniscus and lateral spinothalamic
• Medial lemniscus: Ipsilateral ascent in posterior columns, decussation in medulla, contralateral thalamic projection
• Lateral spinothalamic: Immediate decussation in spinal cord, contralateral ascent to thalamus

Pain Relief

• The Gate Control Theory explanation for rubbing pain relief
• Large-diameter Aß fibers transmit touch information if you were to touch a painful area
• Both pain fibers and touch fibers converge on projection neurons in the dorsal horn according to the Gate Control Theory (Melzack & Wall)
• Inhibitory interneurons modulate this transmission
• Activation of Aß fibers stimulates these inhibitory interneurons
• Descending inhibitory pain pathways (endogenous analgesia): Originates from multiple brain regions
• Periaqueductal gray in the midbrain
• Rostral ventromedial medulla
• Locus coeruleus
• These centers can be activated by stress, expectation/placebo effects, distraction, exercise
• The neurotransmitters involved with Descending inhibitory pain pathways are Endogenous opioids
• Serotonin are also involved
• Norepinephrine is also involved
• The mechanism that Descending fibers synapse on inhibitory interneurons in the dorsal horn
• Interneurons release inhibitory neurotransmitters

Descending and Afferent Nerves

• Afferent Nerves inhibits the transmission of pain signals from primary afferents to projection neurons
• The Afferent Nerves are reduce pain perception is reduced even though nociceptors are activated
• Referred pain in heart attacks: Both cardiac pain and the referred sites share the same spinal cord segments
• Heart pain afferents enter T1-T5 spinal segments if you have pain in that region
• Skin of the left arm also sends afferents to T1-T5 if you have skin in that region
• Upper abdominal/epigastric region sends afferents to similar segments
• Mechanism of referred pain: Visceral and somatic afferents converge on the same second-order neurons in the spinal cord
• The brain cannot distinguish between these converging inputs
• The brain misinterprets the origin as coming from the more common somatic source
• Gender differences in the nervous system that pain sensation
• Women tend to have more diffuse nociceptive inputs from the heart
• Women may have different patterns of convergence in the spinal cord
• Hormonal differences may affect pain processing
• Socio-cultural factors may influence symptom reporting and interpretation
• Women may have more vagal/parasympathetic symptoms (Nausea and indigestion)
• Men typically have more classic somatic symptoms (Left arm pain and chest pressure, in particular)

Specialized Senses

• Sensory systems: Touch and olfaction
• Touch does NOT use specialized non-neuronal cells
• Olfaction USES specialized receptor cells
• Vision USES specialized receptor cells vision
• Description of receptor cells: Olfactory receptor cells, Taste receptor cells and Hair cells and the processes that they use
• Olfactory receptor cells Bipolar neurons with cilia containing odorant receptors
• Taste receptor cells Epithelial cells with microvilli containing taste receptors that synapse with gustatory neurons
• Hair cells Mechanosensitive cells with stereocilia that transduce movement into neural signals
• Aging effects on taste and smell vs touch: Taste and smell are more affected by aging because Taste and smell consists regeneration and longevity
• Olfactory receptor neurons and taste receptor cells have limited lifespans that would range around week(s) and require/depends on continuous regeneration
• Stem cell populations that produce new receptor cells decline with aging receptors Accumulated damage from environmental exposures (pollutants, infections or damage as well in the body) receptors
• Reduced neurogenesis in the olfactory system Decreased production of taste buds and slower turnover

Less Affected Aging

• Aging in reference to taste
• Touch receptors are extensions of long-lived neurons
• Mechanoreceptors don't undergo regular turnover
• Somatosensory pathways are more redundant
• The somatosensory cortex maintains greater plasticity with age
• Number of olfactory receptor genes consist Humans have approx. 350-400 functional olfactory receptor gene and Each olfactory receptor neuron expresses only one type of receptor
• Combination of coding: Combinatorial coding of odor/odors-activation
• Activation: most odorants active multiple receptor types to different degrees and/with that activation
• Each odor produces a unique pattern of receptor
• Combination of patterns:The brain interprets these patterns as distinct odors
• Different concentrations of the same odorant can activate different sets of receptors
• Combination of combinations: Combinatorial coding vastly expands the range of detectable odors beyond the number of receptor types

Taste Receptors

• There are sweet spots in taste
• Taste receptors consist: Humans have only 3 genes for sweet taste receptors but humans have about 25-30 genes for bitter taste receptors in particular as well as well as having the evolutionary advantage of tasting good while others are dangerous due to how they taste but not all the time
• Evolutionary advantage of this difference
• Bitter taste primarily detects potentially harmful toxins and poisons
• Detect toxic compounds from nature which is a survival advantage
• Sweet taste primarily detects calorie-rich foods (sugars)
• Fewer receptor types are needed because there are fewer naturally occurring sugars
• vestibular hair cells and head movement through action movements and hair
• Structure of hair cells consist bundles and stereocilia
• Effects of head movement through stereocilia.