cell bio and neuroscience exam #3

Pseudounipolar neurons

Sensory neurons— One process extending from cell body, sensory receptors at one end and dendrites at the other

Afferent fibers

Send sensory info from skin into CNS

Dorsal root ganglia

Cell bodies outside CNS

Sensory transduction

• Converting the energy of a stimulus into an electrical signal

• Stimulus alters the permeability of ion channels in aferente nerve endings

Mechanoreceptors

Specialized receptor cells that encapsulate afferent fibers; specialized to detect touch, pressure, vibration

Transduction in a mechanosensory afferent

Stimulus causes ion channels to open, resulting in an action potential if threshold is reached

Dermatomes

Innervation arising from a single dorsal root ganglia and its spinal nerve

Axon diameter in afferent fibers

• largest: supply sensory receptors in muscles

• Slightly smaller: touch

• Smaller: pain and temperature

Afferent fibers receptive field

the area of skin surface over which the stimulus results in a significant change in the rate of action potentials

Size of afferent receptive fields

• dense innervation (lots of afferent fibers) have small receptive fields —> smaller 2-point discrimination threshold

• Less densely innervated areas have larger receptive fields

Two-point discrimination

• The minimum interstimulus distance required to perceive two simultaneously applied stimuli as distinct

• Dense innervation = more fibers = smaller 2pt discrimination

Location of stimuli in receptive field

• stimuli at edge of receptive fields spike at slower rate

• Central areas = faster rate

Rapidly adapting afferent fibers

• Detect changes in ongoing stimulation

• Fire rapidly when stimulus introduced, then falls silent after continuous stimulation

Slowly adapting afferents

• Detect spatial attributes, size & shape

• Generate a sustained discharge in the presence of an ongoing stimulus

Types of mechanoreceptors in the skin

Merkle cell afferents, meissner afferents, pacinian afferents, ruffini afferents

Merkle cell afferents

• epidermis (sweat ridges)

• Info about Form and texture (edges, points, curvature)

Meissner afferents

• dermis (but superficial)

• Info about texture object movement across skin (slippage, grip control)

• Rapidly adapting

Pacinian afferents

• deep in the dermis

• Rapidly adapting, very sensitive

• Detect vibrations from objects being gripped, important for skilled tool use

Ruffini afferents

• Dermis

• Slow adapting

• Responsive to internally generated stimuli, involved w muscle receptors for representing finger position (skin stretch)

Mechanoreceptors for proprioception

Muscle spindles, golgi tendon organs, joint receptors

Muscle spindles

In skeletal muscles, signal changes in muscle length

Golgi tendon organs

In tendons to inform CNS about changes in muscle tension

Joint receptors

In joints, appear to be importance for judging the position of the fingers. Little contribution to limb proprioception

Dorsal column-medial lemniscal pathway

• mechanosensory info ascends spinal cord and crosses over at caudal medulla before reaching brain

• Synapses into ventral posterior lateral nucleus of the thalamus, then to primary somatic sensory cortex

Hippocampus

Receives sensory info for learning and memory

Mechanosensory receptors in the face

• Trigeminal ganglion

• Info enters through cranial nerve, not spinal cord, goes to thalamus

Proprioceptive pathways for the upper and lower body

From muscle spindle afferents to spinal cord, to ipsilateral (same side) cerebellum

dorsal spinocerebellar tract

proprioceptive pathway for upper body, info ascends spinal cord to ipsilateral cerebellum

Cerebellum

Regulates the timing of muscle contractions necessary for voluntary movement. Motor learning

Somatic sensory components of the thalamus

• Ventral posterior complex receives info from body and posterior head (VPL) and face (VCM)

• Projects directly onto cortical neurons in the primary somatosensory cortex (SI)

Primary somatosensory cortex

• Broadmann’s areas: 3a, 3b, 1, and 2

• 3b is first step in cortical processing, heavy projections onto areas 1 & 2

Functional changes in somatic sensory cortex following amputation of a digit

Neural plasticity of somatic sensory cortex following allows remaining digits brain regions to adapt

Functional expansion of a cortical representation by repetitive behavioral task

(Monkey experiments) After differential stimulation, a larger region of the cortex contained neurons activated by the digits used in the task

Phantom limb syndrome

• When an amputee has sensation in their amputated limb

• Representation of the face is right next to the somatosensory cortex allows neuroplasticity: the area of the brain corresponding with the face took over the region associated with the amputated hand

• Can be treated with mirror box therapy, visual feedback

Blindsight

• One cannot consciously perceive an object in one side of visual field, but can answer questions about it

• Two pathways link eyes to visual cortex, newer one damaged while primitive one intact

nociceptors

• unspecialized nerve endings that initiate pain sensation

• axons are lightly myelinated or unmyelinated, relatively slow conduction compared to mechanosensory afferents

thermoreceptors vs nociceptors

at a certain temperature, nociceptor reaches threshold and fires meanwhile the thermoreceptor plateaus in response magnitude

first and second pain

first pain is sharp, initial sensation. second pain is delayed, longer lasting.

Type A𝛿 fibers/nociceptors

• fibers are myelinated

• nociceptors specialized for heat and mechanical stimuli

Type C fibers/nociceptors

• fibers are unmyelinated, slower conduction

• nociceptors respond to all types of pain: thermal, mechanical, and chemical (polymodal)

Capsaicin

• ‘hot’ taste

• binds to TRPV1 vallinoid receptor channel

TRP (transient receptor potential)

• TRPV2, TRPA1— chemical irritants (tear gas, exhaust, cigarettes)

• ASIC3— muscle/cardiac pain related to pH changes from ischemia (lack of O₂)

capsaicin as a topical analgesic

Repeated application desensitizes pain fibers, prevents neuromodulators from being released by nerve terminals

wide-dynamic range neurons

• receive all types of input

• also receive visceral (internal) sensory input

• likely involved in Referred pain

Referred pain

feeling pain away from its point of origin (i.e. heart attack in jaw, arm)

dorsal horn, dorsal root ganglia

a visceral pain pathway in the dorsal column-medial lemniscal system. only pathways involving visceral (internal) pain from the pelvis & lower abdomen shown

proves existence of visceral pain pathway: activity in thalamus follows noxious stimuli. after a dorsal column lesion, this activity is abolished (but not by a sham lesion)

midline myelotomy

lesion part of the dorsal column pathway to alleviate visceral pain, inserting needle into the spinal cord

anterolateral system

• pain pathway

• pain and temperature info crosses over immediately in the spinal cord

• ascends all the way to cerebrum

pain and temperature info from the face

descends before ascending in order to cross over at caudal and middle medulla, then reaches cerebrum

lesion in the left lower thoracic spinal cord

• will impair nociceptive afferents from the right, and mechanosensory afferents from the left

• will not impair arms/upper body because info enters above the lesion

lesion in the right lower thoracic spinal cord

• will impair nociceptive afferents from the left, and mechanosensory afferents from the right

• will not impair arms/upper body

location of lesion in spinal cord impacts

If lesion is moved higher up, we would see deficits higher up in the body (arms, upper body)

distinct aspects of pain

anterolateral system has sensory-discriminative processing and affective-motivational processing

sensory-discriminative

location, intensity, quality of noxious stimuli. Spinothalamic tract to somatosensory cortex (S1, S2)

affective-motivational

• unpleasant feeling, fear, anxiety, autonomic activation

• hypothalamus and endocrine system generates stress response (cortisol)

• amygdala generates fear, anxiety

• heightened awareness, alertness

Pain Matrix

brain areas associated with the experience of pain; somatosensory cortex, amygdala, insular cortex, anterior cingulate cortex

pathway that transmits visceral pain info to the brain

dorsal column-medial lemniscal pathway (same as mechanosensory info)

observations that support the discovery of dorsal column visceral sensory projection

• neural response to noxious stimuli

• neural responses reduced by lesions to dorsal column

• infusion of drugs that block nociceptive synaptic transmission blocks neural response to nociceptive information, but not cutaneous

hyperalgesia

following a painful stimulus, subsequent stimuli are perceived as more painful

peripheral sensitization

results from interaction of nociceptors with inflammatory molecules, causing hyperalgesia

inflammatory response to tissue damage

• nociceptors release peptides and neurotransmitters (Substance P, CGRP, ATP)

• non-neuronal like mast cells, platelets, macrophages cells release other molecules (cytokines, histamine, prostaglandins)

• released molecules interact with receptors on nociceptive fibers

allodynia

stimuli that are normally innocuous become painful, occurs immediately after a painful event. can be induced by repeated presentation of a static stimulus feeling increasingly painful

central sensitization

• due to immediate onset, activity dependent increase in excitability of neurons in the dorsal horn of the spinal cord

• Activity of nociceptive afferents that was subthreshold before become sufficient to generate APs in dorsal horn neurons, leading to an increase in pain sensitivity and allodynia

neuropathic pain

increased pain sensitization can persist when afferent fibers or central pathways are damaged (diabetes, shingles, MS, AIDS). chronic, intensely painful experience that is difficult to treat with conventional analgesics

descending control of pain perception

top-down/psychological influence on the pain matrix, perception of pain depends on its context. signals originate in brain and descend to dorsal horn of spinal cord, where they modulate incoming signals.

placebo effect

physiological response varies depending on context accompanying pharmacologically inert “remedy”

gate theory of pain

synaptic interactions w/ the dorsal horn modulate perception of pain

descending pathways that produce pain relief

stimulation of certain midbrain regions results in pain relief. Periaqueductal grey matter (PAG), dorsal raphe, and locus coeruleus

opioid system

opioids are generally inhibitory. exogenous opioids are powerful analgesics, brain regions particularly affected by opioid drugs are sources of descending projections like PAG; dorsal horn also sensitive

endogenous opioid receptors

Mu, Delta, Kappa

endogenous opioid peptides

Enkephalins, endorphins, and dynorphins (agonists to Mu, delta, and kappa)

endocannabinoids

also suppress nociceptive neurons

effect of opioids at the synapse

• closing of Ca²⁺ channels in the presynaptic neuron, decreasing neurotransmitter release

• opening of K⁺ channels, causing efflux and hyperpolarization

opiate effects on respiration

opiate agonists cause respiratory depression

addiction to opiates

euphoria from GABA inhibitory interneurons in the ventral tegmental area. opioids bind to mu receptors, suppressing GABA and increasing dopamine

Desensitization/down-regulation of receptors

results from regular opioid use

withdrawal

symptoms are opposite to physical effects

naloxone

preferentially binds to opioid receptors, stronger affinity

enkephalin neurons in the spinal cord

local circuit interneurons release inhibitory enkephalin (opioid peptide), which projects to dorsal horn and decreases pain perception