MedED BRS Neuro Part 2

  • exteroreceptors - external

  • proprioreceptors - position and movement

    • muscle spindles (changes in muscle length)

    • golgi tendon organs (detect changes in tension in tendons)

    • joint receptors (detect start and end of movement)

  • enteroreceptors - within the bodies internal environmental e.g. movement through the gut and blood pH

  • sensory receptors also split into 5 types: chemoreceptors, photoreceptors, thermoreceptors, mechanoreceptors (pressure changes), nociceptors (detect tissue damage)


  • motor unit - smallest function unit to produce force in muscle contraction - involves a single motor neuron and all the muscle fibres it innervates

    • each motor neurone innervates multiple muscle fibres but each muscle fibre is only innervated by only one motor neurone.


  • gray ramus communicans vs white ramus communicans

  • lacrimal glands secrete tears

  • cranial parasympathetic nerves go to heart to slow it down and go to gut to increase level of digestion


EPILEPSY

  • excitatory and inhibitory neurones that release neurotransmitters

  • GABA transaminase - maintains concentration gradient for GABA reuptake

    • GABA is inhibitory - these bind to chlorine channels causing hypopolarisation of the membrane

  • NMDA receptors - slow component of excitatory transmission, permeable to both sodium and calcium ions

  • AMPA receptor - fast excitatory synapse, only permeable to sodium ions

  • 4 classical drug targets - TIRE

    • Transport proteins - GABA transporters

    • Ion channels - Voltage gated sodium/calcium ion channels

    • Enzymes - GABA transaminase

    • Receptors - GABA/AMPA/NMDA receptors

  • Diazepam

    • Target - GABAa receptor

    • Present on post-synaptic neurone in temporal lobe

    • Effect

      → bind to and increase awareness of GABA activation of receptor

      → changes ion channel confirmation causing chlorine influx

      → decreased chance of seizures

  • Lamotrigine and Pregabalin

    • Both act on ion channels

    • Lamotrigine → voltage gated sodium ion channels

    • Pregabalin → voltage gated calcium ion channels

    • Blocks ion channels meaning less influx off ions

    • With lamotrigine less depolarisation so less neurotransmitter release

    • With pregabalin reduced vesicle exocytosis and neurotransmitter release

  • Levetiracem

    • Target - synaptic vesicle protein SV2A

      • Not part of the classical drug target (non-classical)

      • Important for fusion of vesicle to presynaptic neurone allowing exocytosis to take place

    • Interferes with vesicle fusion reduces exocytosis decreasing the ecxitatory activation of post-synaptic neurone

  • Valproate

    • Drug has multiple targets (broad spectrum)

    • VGSC, GABA transaminase etc…

    • Two potential issues with valproate

      • Teratogenic - avoided in females of childbearing age

      • Non-selective so large number of side effects due to hitting so many targets


AUTONOMIC NERVOUS SYSTEM

  • subdivision of PNS

  • involuntary - not under concious control

  • controls non-skeletal peripheral function

    • viscera, internal organs, smooth muscle and skin

  • autonomic nervous system pathway

    • stimulus detected by visceral sensory

    • sent to the peripheral nervous system and central nervous system

    • motor divison - efferent fibres

      • Split into somatic and visceral motor

      • visceral further split into parasympathetic and sympathetic

  • parasympathetic vs sympathetic

    • often innervate the same tissues but have opposing action

    • sympathetic - fight of flight

    • parasympathetic - rest and digest

  • effect on viscera:

  • Blood pressure

    • Upon increase in blood pressure

      • Baroreceptors detect high bp

      • signals sent to peripheral nervous system

      • parasympathetic neurones to lower bp

      • sympathetic nervous system inhibited

    • Upon decrease in blood pressure

      • Baroreceptors fire less often

      • less signal through visceral motor neurones

      • parasympathetic effect decreases

      • sympathetic system isn’t inhibited - bp increases

  • Autonomic neurones

    • Pre-ganglionic neurones - originate in brain/spinal cord

      • Sympathetic are short by parasympapthetic are long

    • Post-ganglionic

      • sympathetic are long whereas parasympathetic are short

    • Locations of ganglions

      • Symapthetic - close to spinal cord

      • Parasympathetic - close to embedded within effector tissue

  • Neurotransmitters - all preganglionic neurones release ACh

  • Adrenal output

    • Adrenaline hormone from adrenal medulla

    • Into bloodstream and not at synapse (not an NT)

  • Sympathetic control is greater than parasympathetic control

    • Sympathetic trunk - long chains that run parallel to spinal cord

    • Necessary for the following

      • Mass activatoin

      • Co-ordinated fight/flight response e.g. heart rate increasing at the same time the lung constricts

  • Lung doesnt have direct sympathetic control - receives it by adrenaline for bronchodilation for instance

  • Micturition reflex

    • Pressure increase in bladder

    • Sympathetic keeps internal sphincter contracted

    • Pressure continues to rise

    • Visceral sensory info → brain

    • PNS dominates over SNS

    • Detrusor muscle contracts and urine leaves bladder

  • Summary of NTs and receptors

  • ACh Transmission

  • Noradrenaline transmission

    1. Tyrosine converted to DOPA by tyrosine hydroxylase

    2. DOPA converted to dopamine by DOPA decarboxylase

    3. Dopamine packaged into vesicles with dopamine beta hydroxylase forming noradrenaline

    4. Action potential causes calcium influx and exocytosis

    5. Exocytosis and neurotransmitter releaaase

    6. receptor activation

    7. removal