Neuroscience Exam 2

Nociception

The encoding and processing of noxious stimuli by the CNS and PNS

Pain

An unpleasant sensory (physical) and emotional (psychological) experience associated with actual and potential tissue damage

Analgesia

The relief from pain

Noxious Stimuli

Those stimuli that are actually or potentially damaging to tissue

Nociceptors

Neurons responsible for sensing noxious stimuli from the external and internal environment, have free nerve endings that innervate pain

ADelta Fibers

Lightly myelinated

Responsive to mechanical and thermal pain stimuli

Fast, intense pain

C Fibers

Not myelinated

Mechanical, thermal, and chemical stimuli

Throbbing, chronic pain

Visceral Pain

Sparser innervation

Diffuse pain

Referred pain

Mainly mechanical nociceptors

Somatic Pain

Dense innervation

Localized pain

Thermal, chemical, mechanical nociceptors

Hyperglasia

Tissue damage can increase sensitivity to painful stimuli near the site of injury

Prostaglandins

Inflammation causes these to be released to interact with pain receptors to decrease the threshold for depolarization and action potentials, NSAIDs block these to decrease pain

Inflammatory Pain

Damaged tissue, inflammatory, and tumor cells release chemicals that increase the activity of nociceptor afferents

“Inflammatory soup”

Cox2 inhibitors and opioids to treat

Neuropathic Pain

Due to damage to the receptors of the spinal cord/brain regions that process pain

Difficult to treat with analgesics/NSAIDs because not “chemical soup” mediated

Complication of diabetes, shingles, AIDs, MS, stroke, amputation

Sensory Transduction

Through activation of TRP channels, in the free nerve endings of pain afferents

Channel activation by temperature, chemical, or mechanical stimuli allows Ca2+ and Na+ influx to depolarize sensory afferent

Dermatomes

The dorsal root ganglion (DRG) contains the somas sensory afferents from both somatic and visceral structures

At each segment of the spinal cord, each DRG and its associated spinal nerve innervate a territory of the body called this

Referred Pain

Pain afferents from the viscera enter the spinal cord at the same DRG as pain fibers from the skin

Visceral afferents synapse with the same second order neurons in the spinal cord as the pain afferents from the skin, results in confusion in the interpretation of source of pain

NSAIDs

Block prostaglandin, a pro-inflammatory molecule, synthesis

Over the counter, for low-moderate pain

Opioids

Act on a variety of G-protein coupled opioid receptors

Endorphins and opioids extremely important for analgesia

By prescription, moderate-severe pain

Opiate Receptors

Both pre and postsynaptic, located in many areas of the brain and spinal cord

Mu, delta, and kappa receptors, all metabotropic

Activation leads to deceases in neuronal activity

Corneal/Air Interface

Majority of life refraction, not adjustable

Lens

Adjustable refraction for focusing at various distances

Zonal fibers hold in place and connect to ciliary muscles, which help shape

Pupil

Narrows light path

Reduces spherical and chromatic aberration

Improves sharpness

Controlled by iris muscles

Sympathetic and parasympathetic NS control

Optic Disc

In/out point

Vasculature in/out

Retinal axons leave

No photoreceptors

Blind spot

Macula Lutea

High acuity

Yellowish pigment, filter UV light

Site of macular degeneration

Fovea

Center of macula

Highest visual acuity

Most cone photoreceptors

Retinal Circuitry

Neural portion of the eye

Inner wall: retinal neurons

Outer wall: retinal pigment epithelium (contains melanin to prevent backscatter and phototransduction machinery of the photoreceptors)

Convert graded activity of photoreceptors into action potentials that travel to rest of the CNS

Retinal Circuit Neurons

Photoreceptors (cons, rods, change light to current)

Horizontal cells

Bipolar cells

Amacrine cells (only make connections in the retina, light on or off signals)

Ganglion cells (projection neurons, generation of action potentials, send information to brain)

Rods

More numerous

Sensitive to low levels of light (dim)

Cones

Specialized for color and high visual acuity

Highly response to bright light

Retinal Field Size

Fovea: small, therefore high visual acuity and no blue cones

Outside Fovea: large, therefore low visual acuity and red, green, and blue cones

Cones and Color Vision

Single cones do not code for a specific color

Cones code for one of three opsins that respond optimally but not exclusively to the energies of photons of different wavelengths

Color is determined by the relative activity of the different classes of cones in response to a stimulus

Color Blindness

Protanomaly: red-weakness

Deuteranomaly: green-weakness

Protanope: absence of red wavelength response

Deuteranope: absence of green wavelength response

Outer Segment Photoreceptors

cGMP activated Na+/Ca2+ channels that depolarize the photoreceptor, these open and close in response to changing levels of cGMP

Inner Segments Photoreceptors

Potassium channels that hyperpolarize the photoreceptor, leak channels that are always open

Synapse of Photoreceptors

Graded glutamate release depending on the net change in potential between the inner and outer segments, the more depolarized the photoreceptor the more calcium channels are open and the more neurotransmitter is released

Dark Signal Transduction

cGMP activated cation channels open

Na+/Ca2+ influx depolarizes outer segment

K+ efflux hyperpolarizes the inner segment

Net depolarization: Vrest = -40mV

Voltage gated Ca2+ channels open

More glutamate is released

Light Signal Transduction

Light binds to rhodopsin and activates the cis-retinal inside

Light converts cis-retinal to trans-retinal and causes conformational change

Conformational change triggers GTP to activate transducin to release alpha-subunit

Alpha-subunit activates phosphodiesterase that converts cGMP to GMP

Lack of cGMP closes the cation channels, loss of depolarization

Visual Fields

Right visual field is represented by the left side of the retina of each eye and is sent to the left side of the brain, and vice versa for the left

Optic Nerve

Axons only from one eye

Optic Chiasm

Where the optic nerves meet and axons from each eye cross over

Optic Tract

Leaves the optic chiasm and contains axons from both eyes

Visual Cortex

Inputs from the lateral geniculate nucleus of the thalamus project to V1

Where Pathway

Object location

Dorsal stream to parietal lobe

Injury causes optic ataxia

What Pathway

Object identification and recognition

Ventral stream to temporal lobe

Injury causes angosia’s

Outer Ear

Boost sound pressure

Middle Ear

Sound amplification

Inner Ear

Sensory Transduction

Traveling Waves in the Cochlea

Sound cases a traveling wave in the cochlea from the base to the apex

Wave propagates along basilar membrane as vibration

Vibration of the basilar membrane is maximal at the frequency of the sound

Inner Hair Cells

Relays auditory information

Outer Hair Cells

Function in cochlear amplification

Activation of Hair Cells

Movement of tectorial membrane due to basilar membrane vibration causes a shearing force that bends the stereocilia of the hair cell

Sensory Transduction in Hair Cells

Stereocilia are connected by tip links that allow the fast translation of hair bundle movement into receptor potential

Stretch activation cation channel opens, leads to depolarization

10 microseconds

Movement of hair bundle by tectorial membrane opens stretch activated K+ channels in the stereocilia which depolarize the hair cell

Depolarization and Repolarization of Hair Cells

Stereocilia and the cell body of the hair cell are bathed in different extracellular fluids

Stereocilia: high [K+] endolymph from the cochlear duct

Cell body: low [K+] perilymph from the tympanic canal

Thus, K+ flux can cause both depolarization and repolarization of the receptor

Neurotransmitter Release from Hair Cells

Afferent axons that make up the auditory nerve fiber

Presynaptic specializations called synaptic ribbons for rapid neurotransmitter release

Depolarization of the hair cell by K+ activated voltage gated Ca2+ channels and triggers neurotransmitter release

Conductive Hearing Loss

Loss of sound amplification

Swimmers ear, ear infection, ruptured ear drum

Hearing Aids

Amplify sound entering the ear

Microphone, speaker, and amplifier

Capture and amplify sound impinging on cochlea

Aid in conductive hearing loss

Sensorineural Hearing Loss

Irreversible damage to the hair cells or the auditory nerve

Conventional hearing aids do not help because no amount of amplification can make up for a lost ability to transduce or convey sound information

Noise Induced Hearing Loss

Much of the damage is in regions of the cochlea that process speech frequencies

Number of reported cases has doubled in the last 30 years

Cochlear Implants

Bypass hair cells and directly electrically stimulate the fibers of the auditory nerve

Take advantage of the tonotopic organization of the cochlea

Requires functional auditory nerve

From the Ear to the Brain

One hair cell per spiral ganglion cell, preserves the tonotopic map from the cochlea

One hair cell can drive lots of spiral ganglion cells

Vestibular System

Processes sensory information and static position, velocity and direction of movement, acceleration and direction of movement

Mediates rapid autonomic behaviors like reflexive eye movements, postural alignments, and balance

Multisensory integration of visual information, somatosensation, cerebellum

Vestibular Hair Cells - Kinocilium

Vestibular hair cells have a large kinocilium as well as smaller stereocilia that make up the hair bundle

Movement of the bundle toward the kinocilium depolarizes the hair cell

Movement away from the kinocilium hyperpolarizes the hair cell

Otolith Organs

Respond to static head position, tilts, and linear movement (acceleration)

Tilt

Tonic response that lasts for the duration

Acceleration

Transient response that lasts until inertia is overcome

Autonomic Nervous System

Concerned with the maintenance of a constant internal state - homeostasis

Maintains the expenditure and replenishment of resources (metabolic, respiratory)

Controls involuntary functions of smooth muscles, cardiac muscles, and glands

Sympathetic System

Receives output from nearly all segments of the spinal cord

Mobilization of body’s energy resources

Fight or flight

Parasympathetic Motor System

Receives projections only from the brainstem or the sacral spinal cord

Restoration of body’s energy resources

Rest and digest

Visceral Sensory Neurons

Receive sensory information - stretch, pressure, nociception, chemoreception from target tissues

Project to dorsal horn, local interneurons (referred pain) and lateral horn (autonomic reflexes)

Paraganglionic Neurons

Spinal neurons that project to visceral motor neurons in ganglia

Autonomic Innervation of Smooth Muscle

Lacks defined neuromuscular junctions

The axons of sympathetic and parasympathetic motor neuron make varicosities with the cells

The “synapses” are less organized and neurotransmitter can diffuse a great distance from the synaptic cleft

Ionotropic Receptors

Nicotinic acetylcholine (Ach) receptors (nAChR)

Ach binding directly opens the channel and depolarizes postsynaptic cell

Preganglionic to motor neuron synapse

Motor neuron to sweat gland synapse

Fast postsynaptic response

Metabotropic Receptors

Muscarinic acetylcholine receptors (mAchrR)

Norepinephrine (noradrenalin) receptors (adrenergic)

Multiple types and effects depending on associated g-proteions

Motor neuron to smooth muscle, gland synapses

Solitary Nucleus

Brainstem nuclei

Receives visceral sensory input

Integrated visceral sensorimotor reflexes

Reticular Formation

Brainstem nuclei

Collection of nuclei that interact with many system

Autonomic centers that mediate respiratory rhythms, cardiovascular output, gagging, vomiting, laughing, crying

Regulation of Blood Pressure

Changes in BP and oxygenation are sensed by baroreceptors in the carotid body and the aorta

Sensory information is relayed to the spinal cord and solitary nucleus

The solitary nucleus projects to the reticular formation

Reticular formation projects sympathetic and parasympathetic paths

When Increase in BP

Decrease sympathetic output - decrease NE release at the cardiac pacemaker and musculature

Increase parasympathetic output - increase Ach release at the cardiac pacemaker and musculature

Results in decreased heart rate and increased dilation of blood vessels

When Decrease in BP

Increase the sympathetic output - increase NE release at the cardiac pacemaker and musculature

Decrease parasympathetic output - decrease Ach release at the cardiac pacemaker and musculature

Results in increased heart rate and constriction of blood vessels

Head Rush

Sudden feeling of dizziness/disorientation upon standing quickly

Drop in BP upon standing causing sympathetic response, but moving quickly does not give sympathetic system enough time so the brain is briefly deprived of blood/oxygen

Upper Motor Neurons

From motor cortex to interneuron circuits in the brainstem or spinal cord (do not leave CNS)

Lower Motor Neurons

From cranial nerve nuclei or spinal cord to muscle (leave CNS)

Alpha-Motor Nuerons

Project to extrafusal muscle fibers (contraction)

Beta-Motor and Gamma-Motor Neurons

Project to muscle spindles (spindle tension)

Motor Unit

Each alpha-motor neuron innervates several fibers within the same muscle

Each muscle fiber receives input from only one alpha-motor neuron

Unit = one-alpha motor neuron and all its postsynaptic fibers

Fast-Fatigable Unit

Largest alpha-motor neuron

Contact large “pale” fibers

“Fast twitch”

Highest force, fastest response

Few mitochondria, easily fatigued

Brief exertions (sprinting, jumping)

Slow Motor Units

Smallest alpha-motor neurons

Contact small “red” slow fibers

High in mitochondria, myoglobin (red)
Resistant to fatigue

Lowest force

Most common in skeletal muscle

Maintenance of upright posture

Fast, Fatigue Resistance Units

Intermediate size fibers

Slow twitch

Not as fast or fatigable as FF but higher force than S

Walking, running

Force of Muscle Contraction

Number of motor units activated

Type of motor unit activated

Rate of action potentials generated in the motor neurons

Neuromuscular Junction

Consists of the presynaptic boutons of the motor neuron and the postsynaptic end plate of the muscle fiber

End Plate

Specialization of the postsynaptic fiber with membrane “pockets” called junctional folds

Depolarization of the NMJ

Acetylcholine bonds the AChR and depolarizes the postsynaptic membrane

End Plate Potential

Synaptic potential that occurs at the muscle end plate

Decay with distance from NMJ, no active zones

All or nothing contraction

Tetanus

Bacteria releases a toxin that disinhibits alpha-motor neurons allowing them to fire at high rates causing muscle spasms

Primary Motor Cortex

Located in precentral gyrus

Stimulation directly evokes movement

Lowest threshold for initiation of movement

Contains a map for the musculature of the body

Contains a map for movements

L5 Betz Cells

Upper motor neurons

Large neuron somas found in L5

Have the longest axons

Project to spinal cord interneurons and lower motor neurons in the hand

Penfield Maps

Electrical stimulation of the surface of the brain the map location that elicit specific muscle contractions

Body regions that require fine motor control (hands/face) have a lot of cortical representation

Similar to the homunculus in somatosensory cortex

Motor Cortex and Skilled Movement

Takes part in planning movement, executing movement, and adjusting the force and duration of a movement

Hyperkinetic Symptoms

Involuntary and exaggerated movements

Damage to basal ganglia

Huntington’s chorea, Tourette’s syndrome

Hypokinetic Symptoms

Loss of motor ability

Damage to basal ganglia

Parkinson’s disease

Cerebellum and Motor Skill

Important for the acquisition and maintenance of motor skills

Precise timing of movements and movement accuracy/error correction