central synapses Flashcards
explain how a patch clam functions
micropippet 0.5-1um presses against cell membrane
short burst of suction ruptures membrane allowing for measurements and voltage control of internal membrane
Chemical transmitters diversity:
Acetylcholine
Amines- including noradrenaline, dopamine & serotonin
Amino acids- including glutamate & glycine
Soluble gases- including nitric oxide (NO)
what is dales rule/hypothesis?
all axonal branches of a neuron release the same neurotransmitters (single or multiple)
co-release often short neurotransmitter and longer modulatory neurotransmitter also H+ ion release
state proportions of CNS synapses that use glutimate and GABA
Around half of the synapses in the CNS use glutamate which bar glu5 metabotropic receptors are excitatory.
Around a quarter of synapses in CNS use GABA which has exclusively inhibitory effects in adults
Cortical synapses can be classified into two types:
Gray’s type 1 have round vesicles and asymmetrical membrane specializations probably mainly glutaminergic synapses.
Gray’s type 2 have flattened vesicles and symmetric membranes. These are probably mainly GABAergic
which glutimate receptors mediate basal transmission
Basal glutamatergic transmission is largly mediated AMPA/Kainate receptors
how do NBQX and APV affect glutamatergic transmission
NBQX blocks AMPA/kainate receptors APV blocks NMDA receptors
Many synapses may release only one vesicle on average for a presynaptic action potential
-> post synaptic responses can be weak yet variable
A single EPSP is normally not sufficient to pass threshold potential hence to trigger a post synaptic action potential usually requires:
Thus temporal summation is needed to cause downstream AP
Or spatial summation
Obvious overlap
Trains of AP can cause facilitation or depression of synaptic release how can this occur?
Residual Ca2+ in presynaptic terminal increase release probability
Vesicle fusion reduces number of possible release sites, until a new vesicle can be primed for release
Synaptic short term dynamics vary across synapses , even for the same axon targeting different post synaptic neurons.
comment about How GABAergic inhibition occurs and diverity of receptors
GABA-A receptors are permeable to CL- ions and HCO3-
GABA receptors are cys loop family pentamers
At least 16 known subunit forms
GABA taken ub by glia and neurons rather than extracellular breakdown
60% GABA2 receptor type
Glutamate must be made then converted to GABA
where are most GABAergic synapses located?
Gaba ergic synapses occur predominantly on the soma and proximal dendrites.
Perisomatic GABAergic synapses are ideally placed to veto action potentials
how do benzodiazipans affect GABAergic transmission
Synaptic theta subunits containing GABA-ARs are sensitive to benzodiazepines hence the downer effect of drugs.
Benzodiazepines increase frequency of channel opening also slow down the decay of synaptic effects
similarities and differences between transmission at the NMJ and centeral synapses
similarities:
transmission is quantal in nature
ligand gated ion channels
differences
central synapses normally only release 1 vesicle
inhibitory and exititory
short term facilitation/depression affects central synaptic communication more
non cholinergic transmission is usualy terminated by diffusion and re-uptake
explain the general cholinergic projections within the brain
Diffuse projections form basal forebrain and from pontine nucleus
Pontine nucleus sends ascending projections to hippocampus and cerebellum
why in Parkinson’s disease can benztropine be helpful in relief of tremor
Parkinson’s disease benztropine helpful in relief of tremor probably because of cholinergic projections and interneurons in the ventral striatum(part of the basal ganglia)
explain the role a path of most seretonergic projections in the brain
Raphe nuclei project into cortex and also into spinal cord
Involved in regulating ‘mood’ and gating pain perception
outline the main dopaminergic projections pathways in the brain
Substantia nigra -> dorsal striatum (nigo-striatal pathway)
Two projections from ventral tegmental area
One to parts of striatum hippocampus/amygdala
And another cortical pathway primarily frontal pathway
Fourth pathway not on figure projects from arc nucleus and hippocampus projects into bloodstream portal system acts on pituitary gland
What function does dopamine have in the brain?
High dopamine levels for initiating behaviour also burst firing once reward obtained regulate prolactin release thought to be important in positive reinforcement.
Parkinson’s disease selective damage neurodegeneration in substantia nigra- means less power to instigate voluntary movement.
what are the two main pathways of noradrenaline in the CNS
Ascending projections from locus serilius
Mesh of neurons in the lateral tegmental area of the spinal cord project down into the spinal cord and into the cerebellum.
how is noradrenaline synthesized?
Noradrenaline synthesized from dopamine by dopamine beta hydroxylase
what are central adrenergic receptors in the brain and what therapeutic treatments work on these?
Alpha 1&2 and beta 1&2
Beta- adrenoreceptors (propanol) are anti anxiety
Depression- noradrenaline reuptake inhibitors (reboxetine & phenelzine)
what is the main advantage of neuromodulation by metabotropic GPCRs? commonalities in how it functions:
ability to amplify a signal
often conformational change in 3rd cytosolic loop
PKA of then used to phosphorylate receptors/ ion channels
Neuromodulation can occur from non synaptic varicosities along the axon which can release neurotransmitter into the general extracellular space
how can non LTP neuromodulation occur?
presynaptic metabotropic receptors can modulate probability of vesicle release
Peri and extra synaptic metabotropic receptors can modulate a neurons response to synaptic input by:
-Directly modulating the properties of the synaptic receptors
-opening / closing k+ channels to alter a neurons excitability
-Can alter the neurotransmitter uptake properties of near by astrocytes
High frequency tetanus’ increase likelihood of synaptic responses in the PSN initially by a very large amount then the effect stabilizes this stabilizing is causes by LTP how does this occur?
Induction of LTP is mediated by NMDA receptors allows Ca2+ transmission
Mg2+ blocks gate acts as a coincidence detector as channels will only conduct if membrane is somewhat depolarised
NMDA receptors increase APMA receptor activity by activating CaMKII
