Neurochemical Pathways - NT Flashcards
What are the three sources of acetylcholine to be used as a NT in the brain?
- Nucleus basalis of Meynert
- Medial septal nucleus and nucleus of diagonal band of Broca
- Pedunculo-pontine Tegmental Nuc/LateroDorsal Tegmental Nucleus (PPT/LDT)
Where do cholinergic neurons from the Nucleus basalis project to and for what purpose?
What receptor predominates?
to neocortex for conscious perception and cognition
m1
Where do the cholinergic neurons of the middle septal nuclei and DBB project to?
Function?
receptor?
to hippocampus
for learning
m1,3,4
Where do the cholinergic neurons of PPT/LDT project to?
function?
receptor?
to spinal cord and thalamus, then on to cortex
cortical activity during REM- PGO waves while dreaming
m1,3,4
Degeneration in the neurons of NBM will cause…
dementia/alzheimers
Damage to the PPT/LDT or its projections will cause what?
REM sleep disorders
- dreamless sleep
- loss of muscle atonia
- acting out dreams
What nucleus is the source of Histamine?
TuberoMammillary Nucleus (TMN)
Cells in the TMN are mainly active during…
Which receptor is an auto-receptor for Neg FB mechanism?
wakefulness
H3 (pre-synaptic)
From the TMN where do histamine neurons project to?
- highest density to HT (H1)
- to cerebral cortex and cholinergic nuclei (H1)
- to thalamus (H1 and H2)
- to hippocampus, amygdala, striatum, cerebellum
What is the function of histaminergic neurons? How do they activate this?
calm wakefulness
- direct mechanism by activating
- H1 and H2 in thalamus
- H1 in cortex
- indirect mechanism by activating
- H1 of cholinergic neurons in basal forebrain
What will hypoactivation of histaminergic projections cause?
increased sleep
obesity bc histamine can no longer suppress appetite
hyperactivation of histaminergic neurons will cause what?
inability to sleep, night terrors
abnormally high during brain tumors and psychosis
Where are the majority of muscarinic ACh receptors located?
brainstem
What amino acid is dopamine transformed from?
tyrosine
What are the two dopaminergic nuclei?
What do these regions do?
- Ventral Tegmental Area (VTA)
- motivation, reward mechanism
- Substantia Nigra
- motor control
Which dopamine receptors are excitatory and which are inhibitory?
excitatory - D1 and D5
inhibitory D2, D3, and D4
D3 and D5 receptors are mostly where?
hypothalamus
D1 and D2 receptors are mostly where?
corpus striatum
What kind of dopamine receptors are found in the pituitary?
D2
What are the four dopaminergic projections from the VTA/Substantia Nigra?
- mesocortical
- mesolimbic
- mesostriatal
- tuberoinfundibular
The Mesocortical projection from the VTA with dopaminergic neurons goes to where is responsible for what?
Hypofunction of the mesocortical projection pathway will result in what?
to prefrontal cortex
cognition and executive functions
negative ssx of Schizophrenia
The Mesolimbic projection of dopaminergic neurons from the VTA go to…
driving…
Hyperactivation of this will cause…
limbic system, nucleus accumbens
motivation, reward; pleasure and addiction center
positive ssx of Schizophrenia
The Mesostriatal projection of dopaminergic neurons from the SNc goes to …
and is called the…
This playes a key role in…
dysfunction here will cause…
caudate and putamen of striatum
Nigro-striatal pathway
motor control/coordination of body movements
motor ssx of PD
Where is the tuberoinfundibular projection of dopaminergic neurons?
What do they do?
What happens if there is damage here?
from hypothalamus to ant pituitary
TIDA neurons regulate prolactin secretion; D2 on lactotrops gets activated and tonically inhibits prolactin secretion
hyperprolactinemia
What are two drugs that are D2 agonists that can work in the pituitary?
bromocriptine and cabergoline
What is the nuclei sending out NE? What does it look like?
What are NE targets?
Locus Coeruleus
blue spot in unstained brain: neuromelanin with NE
alpha 1 and beta 1 are excitatory
alpha 2 is inhibitory
Where are the noradrenergic projections going to?
What do they each do?
- cortex and thalamus
- attention, focus, alertness
- limbic system - amygdala
- fear, anxiety
- hypothalamus
- NE inhibits VLPO via alpha 2
- cerebellum
- motor learning
Hyperarousal of NE projections will cause
mania
stress
PTSD
anxiety disorders
Hypoarousal of NE projections will cause
ADHD
clinical depression
Serotonergic nuclei in the brain stem are…
This is important for …
Raphe nuclei (specifically Dorsal RN and Median RN)
sleep, mood, appetite
Where do serotonergic projections from Raphe Nuclei go and for what purpose?
- from dorsal RN to cortex and basal ganglia
- wake-sleep cycle
- from median RN to hipoocampus, HT, pituitary, and limbic system
hyperactivation of serotonergic projections will cause
decreased libido
sleep disturbances
decreased serotonergic projections in the amygdala leads to…
in the HT it leads to …
in the pituitary gland it leads to…
- amygdala
- sadness
- HT
- appetite changes (anorexia or hyperphagia)
- pituitary gland
- hormonal imbalance including menstrual irregularities, sleep disturbance
The overall result of decreased serotonergic projections is…
The first line to tx of depression is…
pts with serotonin-NE deficiency will take…
depression
SSRI
SNRI
In depression, what is the change in serotonin receptors that we can see in the brain?
pre-frontal cortex has decreased 5-HT1
entire mid sagittal section has decreased 5-HT2
Where are the orexinergic nuclei and what do they do?
lateral hypothalamus (LH)
orexin/hypocretin - wake-sleep stabilizing NT
stabilizes wakefulness
Orexinergic projections from the LH go throughout the brain, but primarily to…
HT: TMN, VLPO, SCN
cerebral cortex
Locus coeruluous and raphe nuclei
decreased orexinergic projections result in…
narcolepsy
narcolepsy-cataplexy
primary hypersomnia
Where are GABAnergic nuclei located and what does it do?
VLPO - sleep-switch of the brain
damage results in insomnia
GABAnergic axons project from VLPO to…
TMN
LH
PPT/LDT
RN
LC
How does etoh interact with neurochemical pathways?
- inhibits glutamate receptor
- NMDA - slurred speech, memory disruption
- release NE - acts as stimulant
- enhance GABA effect - sedative
- indirect effect on DA path
- excitement, pleasure, addiction
