2.1 Cellular Physiology Of The Brain Flashcards
what are the different components of the central nervous system?
neurones
supporting glia cells (ependymal cells astrocytes, microglial cells and oligodendrocytes)
what is the purpose of glia cells?
to support, nourish and insulate neurones
remove waste
describe the structure of astrocytes
star like structure that has perineuonal feet thar sit on blood vessels that contain gap junctions
what is the function of astrocytes?
structural support Help to provide nutrition for neurones – glucose-lactate shuttle Remove neurotransmitters (uptake) – control concentration of neurotransmitters (especially important for glutamate (toxic) Maintain ionic environment – K+ buffering Help to form blood brain barrier (perineural feet)
what is the function of an oligodendrocyte?
myelinates the axons of neurones in the CNS (similar to schwann cells in the PNS)
unlike the schwann cells a single oligodendrocyte can wrap around multiple different axons simultaneously
what does a microglial cell look like?
long flat nucleus
few processes
what is the function of microglial cells?
resident macrophage of the CNS:
immune function
remove damaged nerve cells
sense increased K+ ions
thought to digest neurofibrillary tangles (Alzheimers)
recognise foreign material and become activated
phagocytosis to remov derbis and foreign material
what is the function of ependymal cells?
ependymal cells line the choroid plexus and secrete CSF into the ventricles
have cilia to move the CSF
describe the energy source of neurones
nutrients transported across the BBB
- glucose transported through the endothelium via GLUT1 and into the neurone from the interstitial space via GLUT3
- astrocytes produce lactate which can be transferred to neurones to supplement the supple of glucose (glucose lactate shuttle)
how do astrocytes help in the regulation of neurotransmitters?
have transmitters for glutamate, helps keep the extracellular concentrations low. as glutamate is toxic in high concentrations
why are astrocytes located near synapses?
to facilitate the termination of synaptic response by mopping up the glutamate and removing it from the synaptic cleft
describe the role of astrocytes in maintaining neurone membrane polarity
high levels of neuronal activity leads to a rise in K+ in the brain ECF
astrocytes take up the K+ to prevent the rising levels depolarising the neurones and causing unwanted activity
what is the function of the BBB?
limits diffusion of substances from the blood to the brain ECF
maintains correct environment for neurones
what forms the blood brain barrier?
tight junctions between the endothelial cells
basement membrane surrounding the capillaries
end feet of the astrocyte processes
describe the diffusion of substances across the BBB
diffusion: water, CO2, O2
Transporter: Glucose (GLUT1), Na+, Cl-, K+, amino acids
why is the CNS described as immune privileged?
CNS inhibits the initiation of the pro inflammatory response of T-cells as too much inflammation in the rigid skull would be harmful
can be seen as the CNS does not undergo rapid rejection of allografts
what are the 4 main sections of a neurone?
axon
cell soma / cell body
dendrites
terminals
describe the process of neurotransmitter movement at the terminal
depolarisation at the terminal opens voltage gates calcium channels, allowing calcium to enter the terminal
vesicles fuse and release the neurotransmitter into the synapse
neurotransmitter diffuses freely across the synaptic cleft and binds to the receptors on the post synaptic membrane
what are the 3 chemical classes of neurotransmitters in the CNS ?
amino acids e.g. GABA, glutamate, glycine
biogenic amines e.g. acetyl choline, noradrenaline, dopamine, serotonin, histamine
peptides e.g. somatostatin, cholecystokinin
what is the major excitatory neurotransmitter of the CNS?
glutamate
what are the main inhibitory neurotransmitters of the CNS?
GABA is the main inhibitory transmitter in the brain
Glycine acts as an inhibitory neurotransmitter mostly in the brainstem and spinal cord
what are the recepetors of glutamate in the CNS?
- ionotropic (ligand gated ion channels). permeable to Na+ and K+ causing depolarisation and increased excitability
- AMPA receptors (Na+ and K+)
- Kainate receptors (Na+ and K+)
- NMDA receptors ( Na+, K+ and Ca2+) - Metabotropic ( g protein coupled receptor )
- either alpha q or alpha i
how do neurotransmitters cause fast excitatory responses in the post synaptic cell?
glutamate binds to ionotropic receptors (NMDA/Kainate/AMPA) on the postsynaptic membrane. Causes depolarisation of the membrane and allows more AP to fire
Increased firing of AP called excitatory postsynaptic potential (EPSP)
what glutamate receptors are present in glutaminergic synapses?
NMDA
AMPA
Describe how AMPA and NMDA receptors work together in the glutaminergic synapses
- AMPA receptors mediate the initial fast depolarisation
- NMDA receptors are activated after AMPA as they need glutamate to bind and the cell to be depolarised to allow ion flow through the channel (ion channel is initially blocked by magnesium)
what is meant by synaptic plasticity?
the change in synaptic strength depending on activity of the synapse. The greater the activity at the synapse the greater the strength of the synapse
what is meant by long term potentiation?
Repeated presynaptic stimulation of a nerve, either naturally or in vitro, that results in the long-lasting increased strength of a synapse and is thought to be necessary for learning and memory formation.
describe how glutamatergic receptors have a role long term potentiation
activation of NMDA receptors allows calcium to enter the neurone. This can upregulate AMPA receptors in the post synaptic membrane
Hence strong high frequency stimuation causes long term potentiation
describe the role of glutamate in excitotoxicity
too much glutamate can cause over stimulation of the NMDA receptors and too much calcium entry into neurones.
too much calcium causes excitotoxicity
in what common pathology is glutamate excitotoxicity seen?
stroke. damaged cells release glutamate, causing over stimulation of NMDA receptors
what triggers an inhibitory post synaptic potential
entry of Cl- into neurones via integral Cl- channels in GABAa and glycine receptors.
how do inhibitory neurotransmitters act?
GABAa and glycine receptors have integral Cl- channels. When the ligands bind, Cl- enters the cell, causing hyperpolarisation and decreased AP firing (inhibitory post-synaptic potential)
what medications bind to GABAa receptors?
benzosdiazepines
barbiturates
How do barbiturates affect the action of GABAa
enhance the response of GABAa receptors to GABA
- previously used as an anxiolytic and sedative
- sometimes now used as an antiepileptic
- rarely used as risk of fatal overdose and dependence and tolerance
how do benzodiazepines affect the action of GABA
Bind to GABAa receptors, increasing the response to GABA
- have a sedative and anxiolytic effects
- used to treat anxiety, insomina, epilepsy
where is glycine released?
by inhibitory interneuornes within the spinal cord and brainstem
describe the mechanism of action of the patellar reflex response
hit patellar tendon stretch quadriceps muscle sensed by muscle spindle afferent neurone sent to spinal cord excitatory neurone releases glutamate motor neurone activated, Ach released from muscle neurone, causes contraction of quadriceps. Reciprocal muscles (Hamstrings) relax. Inhibitory interneurone, glutamate released from muscle spindle onto inhibitory glycenergic neurone. Inhibits the motor neuron to the hamstrings.
name some biogenic amines that act as neurotransmitters in the CNS?
- acetylcholine
- dopamine
- noradrenaline
- serotonin (5-HT)
- mostly act as neuromodulators
- confined to specific pathways
What is the role of ACh in the PNS?
Nicotinic ACh receptors: - neuromuscular junction – ganglion synapse in ANS Muscarinic ACh receptors: – postganglionic parasympathetic
Describe the role of ACh in the CNS
– acts at both nicotinic and muscarinic receptors in the brain
– mainly excitatory
– receptors often present on presynaptic terminals to enhance the release of other
transmitters
describe the cholinergic pathways in the brain
neurones originate in the basal forebrain (nucleus basalis) and the brainstem.
Give perfuse projections to many parts of the cortex and hippocampus
also local cholinergic interneurones in the corpus striatum
what is the role of cholinergic pathways in the CNS?
involved in arousal, learning, memory and motor control
why are cholinesterase inhibitors used to alleviate symptoms of Alzheimers disease?
As degeneration of the cholinergic neurones in the nucleus basalis is associated with alzheimers disease. Cholinesterase inhibitors are used to alleviate symptoms of Alzheimers disease
what are the 3 main dopaminergic pathways of the CNS?
nigrostriatal (motor control)
mesocortical (mood arousal and reward)
mesolimbic (mood, arousal and reward)
what is the underlying neuropathology of parkinsons disease?
loss of dopaminergic neurones from the substantia nigra. Therefore less stimulation of the nigrostriatal pathway and less input into the corpus striatum
what is the 1st line treatment for parkinsons disease?
Can be treated with levodopa - converted to dopamine by DOPA decarboxylase
(AADC)
what is the underlying neuropathology in schizophrenia?
May be due to release of too much dopamine
– amphetamine releases dopamine & noradrenaline
– produces schizophrenic like behaviour
– antipsychotic drugs are antagonists at dopamine D2 receptors
why is carbidopa given alongside levodopa?
to stop levodopa breakdown in the peripheral vascular system, before it reaches the CNS.
Inhibits AADC
where is noradrenaline used in the nervous system
peripherally acts as a transmitter at the postganglionic synapse of the sympathetic autonomic nervous system
- in the CNS acts as a neurotransmitter in the cortex, hypothalamus, amygdala, cerebellum
Operates through G protein-coupled α- and β-adrenoceptors in the CNS and PNS
where are noradrenic neurones located in the CNS?
locus coeruleus in the pons and medulla
what is the function of noradrenaline in the CNS?
increased wakefulness
locus coeruleus is inactive during sleep, activity increases during behavioural arousal.
depression may be associated with deficiency of NA
how do amphetamines increase wakefulness?
increases release of noradrenaline and dopamine
what is the function of 5-hydroxytryptamine?
also known as serotonin, functions are to increase wakefulness and effect mood.
what is the function of the raphe nuclei?
Found in the brain stem, they have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. Function as autoreceptors in the brain and decrease the release of serotonin.
what are SSRIs?
SSRIs (serotonin selective reuptake
inhibitors). Used in the treatment of depression and anxiety disorders
