lecture 16 Flashcards
(17 cards)
where do DA neurons in the VTA project
nucleus accumbens, prefrontal cortex, olfactory tubercle, amygdala
what is dopamine modulated by
dopamine is modulated by nicotinic acetylcholine receptors
- important for the indirect path
therefor nicotine can reduce some tremors in parkinsons
self administration of nicotine in mice
slow release delivery system
made lesions in nucleus accombens by using 6-OH dopamine and extinguishes nicotine self administration
what is the receptor in nicotine addiction
a4 nAChR
- mesolimbic dopaminergic pathway
upregulation of chronic nicotine use
chronic nicotine upregulates nicotine binding - more nAChR in brain areas
where afre the changes in a4 nAChR expression
VTA- DA and GABA
SNC - DA
SNR- GABA
chronic nicotine on GABA
chronic nicotine increases a4 receptors in GABAergic and not dopaminergic neurons
increases basal firing of GABA and response to nicotine
regular levels of Ach now has more receptors so GABAergic neuron is more sensitive to nicotine and fires more
GABA effects on dopamine
more GABA firing shuts off dopamine neurons
dopaminergic neurons have decreased basal firing and response to nicotine
circuit based mechanism of tolerance of reward
increased sensitivity of GABA neurons to ACh results in lower basal firing of dopamine so theres less activation of nucleus accumbens (suppression of background reward) which leads to graving for nicotine
need more of it to get same levels of activation
SUMMARY of chronic nicotine exposure
upregulates nACh in GABAergic neurons (VT)
no effect on nAChR levels in DAergic neurons (VTA)
results in lower basal DA release and suppression of DA release when exposed to acute nicotine
difference between cocaine and nicotine
similarity: both interact with VTA DA to NA (same path of craving and tolerance)
difference: nicotine affects # of receptors but cocaine effects amount of transmitter released (reuptake inhibitor)
activation of specific neural circuits triggers sleep and wakefulness
wake up cat: activating ACh neurons in reticular activating system
put cat to sleep: slow repetitive stimulus in thalamus
decreased sensation and muscle paralysis during REM sleep
REM sleep: eye movement but no body movement
dorsal column nucleus neurons are inhibited by glycine and cannot respond to somatic sensory stimuli
lower motor nuerons are inhibited
Ach leads to disinhibition of GABA early on
which cortical regions change activity in REM sleep
activated- anterior cingulate cortex, amygdala, parahippocampul gyrus, pontine tegmentum
inactivated- posterior cingulate cortex, dorsolateral prefrontal cortex
difference between spindle sleep and awake
thalamic neuron activity is locked into bursting mode that doesnt correspond to coherent sensory or other activity thus leaving the cortex active but not able to process info
bursting sleep AP
excitation/inhibition comes from intrinisc current in thalamic cortical neuron
when hyperpolarized it wants to depolarize
there is depolarization dependant inactivation of H and T so both shut off- neurons will burst on their own through interaction of hyperpolarized activation current
switch from burst to tonic mode
- 5HT, NA and histimine shift activation curve to be more depolarized and keep cell depolarized
- Ach acts on mACh receptors to reduce GABA inhibition from thalamic reticular interneurons = less hyperpolarized
by removing tonic hyperpolarization ICaT is inactivated and bursting and Ca spikes eliminated
