cholinergics Flashcards
Ach expression requires what 3 proteins?
ChAT (Cholinetgic Acetyl Transferase)
VChAT (Vesicular Acetylcholine Transporter);
Choline Transporter 1
what 3 structures and what interneurons contain cholinergic neurons?
Basal forebrain
Mesopontine tegmentum
Brainstem, Cranial nerves, and motor neurons
interneurons:
- striatum
~ rare in cortex
What are the main cholinergic neurons in the basal forebrain?
Ch1: Medial septum Ch2: Vertical End Ch3: Horizontal Diagonal Band of Broca's Ch4a: Basal Nucleus of Meynert Ch4p: Nucleus Inomminate
Outside basal forebrain…
Ch5/Ch6: Mesopontine nuclei
poorly defined structures and tangled in white matter tracts
What are the reciprocal input/outputs in the forebrain and what system do they project to?
INPUT -vta -thalamus -hippocampus -amygdala ~supra-mammillary nuclei --> only input (not reciprocal)
OUTPUT
- vta
- thalamus
- amygdala
- hippocampus
ascending sensory and motor info to limbic system
describe the connectivity of cholinergic neurons
Ch1/2: hippocampus via the fornix
Ch3: entorhinal, piriform, olfactory bulb –> Medial Septum and Vertical End of Broca’s connect to orexin and hypocretin neurons in Lateral Hypothalamus
remember: (l)HOPE
Ch4: basolateral amygdala, neocortex
What is the relevance of the medial septum in basal forebrain?
MS is pivotal node within an ascending pathway from the brainstem and the hypothalamus that conveys sensory and motor information to the limbic system.
Characteristics of a cholinergic basal forebrain neuron:
- single axon
- synaptic (point to point) AND volumetric transmission
- and - innervation
- acts via nicotinic and muscarinic receptors
What is the effect of Ach in regulation of attention for goal associated information?
Ach is released after cue detection –> Disturbs normal function through Ach desynchronization –> Attention is orientated to cue as desynchronization provides opportunity for modulated input and neuronal response
What are the two types of navigation and how to they work?
Egocentric - location in relation to one’s self completely independent from environment
experiment = place avoidance (habituation -> training -> test)
Allocentric - location that is dependent and relative to environment; independent of self
What is the function of the Cholinergic Basal Forebrain?
Attention –> at cellular level
Responsible for mechanisms of synaptic plasticity, learning, memory, reinforcement and extinction
Allows executive functions: complex/associative memory, conscious planning, reasoning, experience-dependent decision making
^^ in relation to stimulus ie. shock
What impact does cholinergics and release of Ach have on memory formation and routine behaviour?
The process of learnt, routine, behaviour is a result of prior experience and exposure to a stimulus. The act of calling on an experience and bringing it to consciousness later in time requires, an association to such an experience, and a “retrieval cue” to elicit the memory. This “cue” is the result of Ach release and disturbance during the previous exposure to the stimulus.
eg. Routine behaviour like making the decision to cross the street.
Physiology of Ach: what are Ach firing patterns during different activity levels?
Cholinergic neurotransmission is inhibitory during quiescence (rest)
Cholinergic neurotransmission is excitatory during simultaneous post-synaptic activity (stimulus)
By reducing the excitability of less active neurons and enhancing that of the more
active ones –> cBF neurons increase the signal:noise ratio of incoming information.
Low GLU levels means suppression of transmission while greater input of GLU excites neuromodulation …
What is dementia? What constitutes as AD?
Dementia is the decline of intellectual function that is severe enough to impair daily activity.
AD is the present of both memory loss and another deficit ie. language impairement, attention (cholinergic neuron loss), executive function, or visuospatial ability.
Alzheimer’s disease atrophy to brain:
- Atrophy to cortex (planning, thinking, imagination impairment)
- Atrophy to hippocampus (short memory)
- Atrophy to Basal Forebrain (memory and attention)
- Ventricular Enlargement
Pathological features of AD:
Tau Protein tangle = neurofibrillary tangles
Amyloid-Beta deposition = amyloid plaques
Cholinergic neuron loss in basal forebrain = ~75% loss relative to healthy brain
