cortical modulatory networks Flashcards
what is a CMN?
system of brain regions and neurotransmitter pathways that modulate (i.e., regulate or fine-tune) the activity of the cerebral cortex, rather than directly driving it
what are the multiple scales of neuromodulator actions?
decision making (layer/dendrite)
attention (brain/circuit/layer)
sleep (brain/circuit/layer)
mood (neuron/circuit/layer)
learning/memory (neuron/dendrite/syanpse)
all of which work at different time scales e.g decision making=milliseconds, learning/memory=days
where is acetylcholine released from?
basal forebrain complex
- medial septum (MS)
- diagonal band of broca (DB)
- nucleus basalis (nBM)
brainstem system (pontpmesencephalotegmental complex)
- laterodorsal pontine tegmentum (LDT)
pedunculopontine tegmentum (PPT)
what is the role of acetylcholine?
alerting general brain excitability during arousal, sleep/wake, attention
has roles in learning and memory
brainstem systems regulate excitability of thalamic sensory relays
where do basal forebrain complexes project to?
hippocampus, neocortex, cortex and amygdala
where do brainstem systems project to?
thalamus, basal forebrain, cerebellum and spinal cord
disorders associated with acetylcholine
cognitive decline and alzheimers disease
where is noradrenaline released from?
produced by locus coeruleus (pons) and neurons of the LC release NA
1 LC neuron can make more than 250,000 synapses
only 12,000 neurons on each side (small)
what is the role of noradrenaline?
attention
arousal
sleep/wake
learning
anxiety
mood
ascending projections of the LC
hippocampus, amygdala, neocortex, thalamus and cerebellum
descedning projections of the LC
trigeminal nucleus and dorsal horn
brainstem and spinal motor nuclei
what is the LC activated by?
novel and unexpected stimuli
disorders associated with noradrenaline
mood disorders- noradrenaline reuptake inhibitors (reboxetine)
MAO inhibitors- reduce degradation of noradrenaline
where is serotonin released from?
9 raphe nuclei in brainstem which release 5-HT (serotonin)
each nucleus projects to different brain regions
descedning projections of serotonin
regulation of nociceptive inputs (e.g medulla)
ascedning projections of serotonin
cells fire most during wakefulness/arousal (e.g amygdala, cingulate gyrus, hippocampus)
what system is serotonin apart of?
the ascedning reticular activating system (ARAS) which is important for regulation of sleep/wake and different stages of sleep
role of serotonin
regulation of mood and emotion
disorders associated with serotonin
anxiety disorders, mood disorders (depression, bipolar)
prozac (fluoxetine)- SSRIS prolong action of serotnin
MAO inhibitors
where is dopamine released from?
substantia nigra for motor control and ventral tegmental area (VTA) where projections are mainly to fronral cortex, limibic areas and nucleus accumbens
what is the role of dopamine?
reward system- reinforcement of certain behaviours
disorders associated with dopamine
psychiatric disorders (schizophrenia)- D2 antagonists
addiction
syanptic transmission in circuits
within the hippocampus there is feedforward and feedback inhibition
e.g presynaptic releases L-GLU activated AMPA causes EPSP
muscarinic (metabotropic) acetylcholine receptors
M1,3,5 – depolarisation,
increase action potential frequency
M4 (2?)– decrease transmitter release
nicotinic (ionotropic) acetylcholine receptors
alpha4beta2 – transmitter release
alpha 7 – transmitter release/plasticity
plasticity and muscarinic acetylcholine receptors
induction of LTP at CA1 synapse
M2 muscarnic knock out in transgenic animal
this causes a decrease of plasticity
therefore M2 regulates plasticity
with gallamine (M2 antagonist) there is also a decrease in plasticity
plasticity and nicotinic acetylcholine receptors
alpha 7 agonist activating receptors produced LTP
alpha 4/beta 2 activation produces a decrease in plasticity
thalamic tonic firing dependent on modualtors
promoted by ACh, NA, 5HT and histamine
neuromodulators depolarise thalamic neurons by:
reducing leak K currents
ehancing non-specific cation currents
this inactivates T-type Ca2+ channels, preventing burst firing
thalamic neurons fire tonically, which supports faithful sensory relay during alert, awake states
thalamic burst firing dependent on modualtors
in absence or reduction of neuromodulatory input, thalamic neurons hyperpolarise
this de-inactivates T-type Ca2+ channels
when depolarised from this hyperpolarized state, the neuron fires a low-threshold burst of action potentials
burst firing acts as a “gating” mode, suppressing or modulating sensory transmission
needed for sleep, disengagement and sensory gating
