cortical modulatory networks

Question 1

what is a CMN?

Answer 1

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

Question 2

what are the multiple scales of neuromodulator actions?

Answer 2

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

Question 3

where is acetylcholine released from?

Answer 3

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)

Question 4

what is the role of acetylcholine?

Answer 4

alerting general brain excitability during arousal, sleep/wake, attention
has roles in learning and memory
brainstem systems regulate excitability of thalamic sensory relays

Question 5

where do basal forebrain complexes project to?

Answer 5

hippocampus, neocortex, cortex and amygdala

Question 6

where do brainstem systems project to?

Answer 6

thalamus, basal forebrain, cerebellum and spinal cord

Question 7

disorders associated with acetylcholine

Answer 7

cognitive decline and alzheimers disease

Question 8

where is noradrenaline released from?

Answer 8

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)

Question 9

what is the role of noradrenaline?

Answer 9

attention
arousal
sleep/wake
learning
anxiety
mood

Question 10

ascending projections of the LC

Answer 10

hippocampus, amygdala, neocortex, thalamus and cerebellum

Question 11

descedning projections of the LC

Answer 11

trigeminal nucleus and dorsal horn
brainstem and spinal motor nuclei

Question 12

what is the LC activated by?

Answer 12

novel and unexpected stimuli

Question 13

disorders associated with noradrenaline

Answer 13

mood disorders- noradrenaline reuptake inhibitors (reboxetine)
MAO inhibitors- reduce degradation of noradrenaline

Question 14

where is serotonin released from?

Answer 14

9 raphe nuclei in brainstem which release 5-HT (serotonin)
each nucleus projects to different brain regions

Question 15

descedning projections of serotonin

Answer 15

regulation of nociceptive inputs (e.g medulla)

Question 16

ascedning projections of serotonin

Answer 16

cells fire most during wakefulness/arousal (e.g amygdala, cingulate gyrus, hippocampus)

Question 17

what system is serotonin apart of?

Answer 17

the ascedning reticular activating system (ARAS) which is important for regulation of sleep/wake and different stages of sleep

Question 18

role of serotonin

Answer 18

regulation of mood and emotion

Question 19

disorders associated with serotonin

Answer 19

anxiety disorders, mood disorders (depression, bipolar)
prozac (fluoxetine)- SSRIS prolong action of serotnin
MAO inhibitors

Question 20

where is dopamine released from?

Answer 20

substantia nigra for motor control and ventral tegmental area (VTA) where projections are mainly to fronral cortex, limibic areas and nucleus accumbens

Question 21

what is the role of dopamine?

Answer 21

reward system- reinforcement of certain behaviours

Question 22

disorders associated with dopamine

Answer 22

psychiatric disorders (schizophrenia)- D2 antagonists
addiction

Question 23

syanptic transmission in circuits

Answer 23

within the hippocampus there is feedforward and feedback inhibition
e.g presynaptic releases L-GLU activated AMPA causes EPSP

Question 24

muscarinic (metabotropic) acetylcholine receptors

Answer 24

M1,3,5 – depolarisation,
increase action potential frequency
M4 (2?)– decrease transmitter release

Question 25

nicotinic (ionotropic) acetylcholine receptors

Answer 25

alpha4beta2 – transmitter release alpha 7 – transmitter release/plasticity

Question 26

plasticity and muscarinic acetylcholine receptors

Answer 26

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

Question 27

plasticity and nicotinic acetylcholine receptors

Answer 27

alpha 7 agonist activating receptors produced LTP alpha 4/beta 2 activation produces a decrease in plasticity

Question 28

thalamic tonic firing dependent on modualtors

Answer 28

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

Question 29

thalamic burst firing dependent on modualtors

Answer 29

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