Case 7 Flashcards
What is the main efferent neurotransmitter of PNS?
Acetylcholine
What is the acetylcholine precursor?
Acetyl coenzyme A and choline
What is the catalyst in the synthesis of Acetylcholine?
Choline acetyltransferase (CAT)
What is the enzyme that hydrolyses Acetylcholine?
Acetylcholinesterase (AChE)
Broken down into acetate and choline (choline is reabsorbed via sodium-choline transporter)
What is Nicotinic ACh receptors?
Non-selective cation channels that generate excitatory postsynpatic responses
Where are nAChR found?
Ganglion between pre and postganglionic nerve
What are Muscatinic ACh receptors?
Metabotropic and mediate most of the effects of ACh in the brain
They are highly expressed in the striatum
What is the main excitatory transmitter in the CNS?
Glutamate
What are the precursors of Glutamate?
Glucose or glutamine
What releases glutamine?
Glial cells
What is the enzyme that converts glutamine into glutamate?
Mitochondrial enzyme glutaminase
What enzyme converts glutamate into glutamine in glial cells?
Glutamine synthetase
What is the ionotropic receptors of Glutamate?
NMDA, AMPA, and Kainate
Which Glutamate receptor can increase calcium concentration in postsynaptic neurons?
NMDA - leading to activation of intracellulaire signalling cascades
Which cation blocks the NMDA pote during hyperpolarisation?
Magnesium
Depolarisation pushes it out to allow flow of cations (requires glycine)
What is the difference between NMDA and AMPA synaptic currents?
NMDA are slower and longer-lasting than those produced by AMPA/Kainate receptors
What do metabotropic glutamate receptors do?
They cause an inhibition of postsynaptic calcium and sodium channels decreasing the excitability of postsynaptic cells
What is the major inhibiting neurotransmitter in CNS?
GABA or Glycine
What forms GABA?
Glutamate via reaction catalysed by glutamic acid decarboxylase (GAD) - found one GABAergic neurons
Where is GABA abundant?
Nigrostriatal system
What converts GABA to succinate?
GABA transaminase
What are the two groups of GABA postsynaptic receptors?
Ionotropic - GABA(A) and GABA(C) > causes hyperpolarisation via increase of Chloride ion permeability
Metabotropic - GABA(B) > cause hyperpolarisation via activation of Potassium channels and inhibition of calcium channels
Where is glycine abundant?
Spinal cord grey matter of ventral horn
What produces Dopamine?
L-DOPa via reaction catalysed by DOPA decarboxylase
What is a DAT?
Sodium dependent Dopamine transporter in glial cell membranes used to re-uptake dopamine from synaptic cleft
Which enzymes are involved in dopamine breakdown?
Monoamine oxidase (MAO)
Catechism-O-methyltransferase (COMT)
How does cocaine produce its psychotropic effects?
Blocking DAT hence increasing synaptic cleft concentration of Dopamine
Where does the dopaminergic system arise?
Midbrain
What makes the substantia Nigra appear dark?
Neuromelanin in dopaminergic receptors
Where does the nigrostriatal pathway mainly arise from?
substantia nigra pars compacta and projects to striatum (caudate and putamen)
This is the primary input into basal ganglia system
What does dysfunction of nigrostriatal pathway cause?
Movement disorders such as Parkinson’s Disease
Which dopamine pathways arise from ventral tegmental area?
Mesolimbic - VTA to limbic structures (pathway for reward and addiction)
Mesocortical - VTA to prefrontal cortex (pathway for working memory and attentional aspects of motor imitation)
What are dopamine receptors?
G-protein coupled receptors
Subtypes activate or inhibit adenylyl cyclase
Dopamine also acts on adrenoreceptors
How is movement modulated?
By a group of nuclei deep in the cerebral hemispheres known as Basal ganglia
What does basal ganglia do?
Facilitate initiation of motor program that express movement and suppress competing motor program that interferes with expression of sensory-drive or goal directed behaviour
What are the nucleus of the basal ganglia called?
Caudate and Putamen (Corpus Striatum)
Globus pallidus
How does the basal ganglia influence movement?
It regulates the activity of the UMN
What type of movement does the loop formed by basal ganglia, substantia nigra and subthalamic nucleus cause?
Voluntary
Problem in any part of the loop causes problems with smoothly switching between commands that start movements and those that end movements
What are the largest input into basal ganglia?
Corticostriatal pathway - cortex to corpus striatum via internal capsule
Which cortical areas do not project to corpus striatum?
primary visual and auditory cortices
What is the destination of input from cortex?
Medium spiny neurons in corpus striatum
Most input is excitatory
What is the main output of basal ganglia?
Globus pallidus and Substantia Nigra pars Reticulata
Where do axons from the basal ganglia go?
Globus pallidus and substantia nigra reticulata
What are the circuits formed in basal ganglia?
Cerebral cortex to medium spiny cells (Glu)
Interneurones to medium spiny cells (small IN are GABA; big IN are ACh)
Substantia nigra par compacta to medium spiny cells (dopamine)
Why are medium spiny neurones usually silent?
Because they require excitatory inputs simultaneously from cortical and nigral neurones
What does dopamine and glutamate do in the basal ganglia circuits?
Modulate synaptic strength
What is the purpose of direct pathway of voluntary movement?
Stimulate muscle movement
What is the direct pathway voluntary control of movement?
Primary motor cortex to putamen (Glu) > increase putamen to GPi (GABA) > decrease GPi to thalamus (GABA) > increase thalamus to primary motor cortex (Glu)
What is the function of the indirect pathway for voluntary motor control?
Inhibits muscle movement
What is the indirect pathway voluntary control of movement?
Primary motor cortex to putamen (Glu) > increase putamen to GPe (GABA) > decrease GPe to Subthalamic nucleus (GABA) and GPi (GABA) > increase subthalamic to GPi (Glu) > increase GPi to Thalamus (GABA) > decrease thalamus to primary motor cortex (Glu)
How is muscle movement stimulated?
Primary motor cortex signals substantia nigra compacta which then simultaneously stimulates direct pathway and inhibits indirect pathway for muscle movement
What normally happens at dopamine receptors?
D1R - activation causes increase in dynorphin and stimulates direct pathway [excites Adenylyl cyclase to form cAMP from ATP]
D2R - activation decreases enkephalin, causing inhibition of indirect pathway [inhibits adenylyl cyclase to prevent cAMP from ATP]
How is eye movement controlled by basal ganglia?
Corpus striatum to substantia nigra pars reticulata to UMN in superior colliculus
What is the ansa lenticularis and lenticular fasciculus?
Carries fibres from Globus Pallidus to thalamus
Join to form thalamic fasciculus
What is the subthalamic fasciculus?
Carries fibres of indirect pathway from GPe to Subthalamic nucleus and Subthalamic nucleus to GPi
What are the three lobes of the cerebellum?
Anterior, posterior and flocculonodular
What are the three main tracts of the cerebellum?
- Cerebrocerebellum - high skilled movement for extremities
- Vestibulicerebellum - input from vestibular nuclei to regulate movement underlying posture and equilibrium
- Spinocerebellum - input directly from spinal cord; lateral part = movement of distal muscles and vermis = movement of proximal muscles and eye movements (in response to vestibular input)
What carries output from cerebellum?
Superior cerebellar peduncle (decussates In midbrain at the level of inferior colliculi)
What does the middle and inferior cerebellar peduncle carry?
Inputs to cerebellar
What are the deep cerebellar nuclei?
Dentate- input from lateral cerebellar hemispheres
Interposed - (emboliform and globose nucleus) Input from the intermediate cerebellar hemisphere
Fastigial - input from vermis and flocculus (fibres leaving inferior vermis and flocculi project to vestibular nuclei)
What is the largest input to cerebellum?
Primary motor and premotor cortices (go to cerebrocerebellum)
What are other inputs to cerebellum?
From cerebrum:
• Primary and secondary somatic sensory cortices, secondary visual regions
From periphery:
• CN VIII vestibular axons and axons from vestibular nuclei in medulla to vedtibulocerebellum
• dorsal nucleus of Clarke in spinal cord to spinocerebellum
Others:
• inferior olive and locus cerulean in brain stem (for learning and memory functions)
Where do the cortical pathways relay before entering cerebellum?
Pontine nuclei >enter contralateral cerebellum hemisphere via middle peduncle
What is the nucleus of Clarke?
Group of relay neurons innervated by proprioceptive scones from periphery
