6. Mechanism of Arousal: Brain Arousal Systems Flashcards
What is consciousness recognized as?
Has two parts: arousal (being awake) vs. awareness (conscious processing of inputs)
What is a coma?
neither being awake or aware
has eye/head motions
What is a persistent vegetative state?
eye/head motions and physiologically identifiable sleep/wake cycles appear
no evidence of awareness or verbal responses
What is a minimally conscious state:
eye/head motions, sleep/wake cycles, awareness, and verbal responses (INCONSISTENT)
reproducible evidence of awareness- ability to respond to simple commands; inconsistency related to plasticity
limited or absent communication
What are the steps in the hierarchy of consciousness (least to most alert)? What does it say about the basis of consciousness?
coma–> arousal/wakefullness (sleep/wake)–> awareness–> alertness
- different levels of consciousness/awareness are result of diff. levels of cortical excitation
- moving from arousal/wakefullnes to awareness requires additional excitation
- moving from awareness to alertness (full awareness) takes another layer of excitation to achieve
How does the nature of injuries alter consciousness permanently? what is it usually from?
it is a misconception that comatose state results from damage to cerebral cortices; damage must be MASSIVE and bilateral
disruptions of consciousness typically result from smaller lesions in brainstem, midbrain, and hypothalamus (lower brainstem area)
What evidences from patients in persistent vegetative state tells us about the nature of consciousness?
you can see marked loss of neurons in Midbrain, pons, etc. (so lesions from lower brainstem, not cortex)
AKA- brainstem regions are CRITICAL for arousing the cortex
Activation of what is required for arousal and awareness?
activation of the cortex!!
but cortex lacks an intrinsic mechanism for activation so relies on input from other parts of the brain
What is the function of the arousal systems?
5 NTs associated with them
core= EAA system (associated with traditional RAS)
also have cholinergic, noradrenergic, serotonergic, and dopaminergic arousal systems
What is the EAA arousal system associated with? what does it arise from?
associated with the traditional RAS
Anatomy: arise from parabrachial nuclei (in mid-ventral portion of medulla and midbrain); loose collection of neurons and fiber tracts; postsynaptic pathways are complex
What are the inputs to the Reticular Activating System?
trigeminal, auditory, visual
all ascending sensory tracts send information to the RAS!!
What are the characteristics of inputs to RAS? what is lost?
there is sufficient convergence of input to neurons of RAS that MODAL SPECIFICITY is lost!!–> brain only knows something happened, but not what happened (event detector)
so neurons of RAS respond equally well to multiple sensory modalities
What are two output pathways from the RAS? via what?
- Dorsal pathway– via non-specific nuclei of thalamus (including INTRALAMINAR NUCLEUS OF THALAMUS); from there diffuse pathways to all higher levels
- Ventral Pathway– via basal forebrain and hypothalamus (bypasses thalamus); from there, diffuse pathways to all higher levels!
Where is the parabrachial nuclei located? what are they crucial for?
in the pons (medial, intermediate, and lateral)
crucial for activation/arousal
What are the inputs for the parabrachial nuclei?
similar to RAS–> all/most of sensory inputs to body
What are the outputs from parabrachial nuclei?
EXCLUSIVELY via ventral pathway!!
extensive, very diffuse innervation of entire cortex
What is the major NT utilized by both parabrachial and RAS neurons?
EAA/glutamate (for both dorsal and ventral pathways)
Within the RAS, what do neurons release?
There is a substantial number of interneurons (intrinsic to RAS) that release GABA
Also have neuronal population that releases ACh
What is the EAA systems general role in arousal?
regardless of path (dorsal or ventral), it appears to provide a baseline excitation that is crucial to cortical activity
Within the cholinergic arousal system, what input and outputs are sent to and from the pedunclopontine tegmental and laterodorsal nuclei (PPT/LDT)?
INPUTS: like RAS, receive so much that modality-specifci info is lost
OUTPUTS: via dorsal and ventral pathways used by RAS
What is the major neurotransmitter used in the pedunclopontine tegmental and laterodorsal nuclei?
part of cholinergic arousal system, so ACh
What is the cholinergic arousal systems role in arousal?
regardless of path (dorsal or ventral), it also appear to provide a baseline excitation that is crucial to cortical activity
activity in cholinergic inputs from pons is also associated with arousal and awareness
What happens when there is damage to the PPN/DLT nuclei?
doesn’t necessarily cause coma, but does produce SEVERE cognitive deficits that are associated with generalized slowing of cortical processing (can wake tho)
Alzheimers
decline in all cognitive processing
What is required for normal arousal and establishment of sleep wake cycles?
full function of both EAA and ACh arousal systems
Where are the cell bodies of the noradrenergic system located? what is this system the major source of?
at the locus coereuleus in the pons
major source of NE in brain
Where do the inputs to the locus coereuleus come from?
major source= brainstem nuclei, especially Paragigantogocellularis N. (in rostral medulla)= sensory info
PAG= periaqueductal grey
higher centers (hypothalamus, amygdala, cortex)
What is different about the inputs coming into the locus coereuleus?
the information is processed a bit more, existence of it depends on function of EAA/ACh core already being in place
What are the outputs from the locus coereuleus?
have both ascending and descending
Ascending fibers: dorsal and ventral axons join axons fof the RAS/parabrachial/PPT/LDT in dorsal and ventral pathways
What do the ascending fibers from the Locus coereuleus become?
dorsal noradrenergic bundle
What are the functions of the locus coreuleus NE Arousal system?
STARTLE and ALERTING response on EEG (now aware of specific event**)
sleep-wake
behavioral vigilance
Where are the cell bodies of the serotonergic system located?
raphe nuclei
Where are the inputs to serotonergic system coming from?
Sensory- from spinal cord (fine proprioception)
trigeminal sensory nuclei
Periaquaductal grey- pain control
What are the outputs from the raphe nuclei/ serotonergic system?
both dorsal and VENTRAL* paths are used
ventral strong through hypothalamus!!
What are the functions of the serotonergic system?
QUIET AWARENESS* (not focused on anything specific, but aware of whats around)
regular awareness
other functions: mood and affect, modulation of pain
To get from arousal/Wakefullness to awareness, what do you need?
NE and Serotonin arousal systems
What is the last layer important to get to full alertness?
Dopaminergic Arousal system
Where are the cell bodies for the dopaminergic system located?
ventral tegmental area
What is the function of the ventral tegmental area?
VTA (w substantia nigra) provides a dopaminergic input that is important for functions including: cognitive function, motor activity, emotion
alertness in response to novel stimuli (brain arousal function)
What illness is associated with a disruption of DA?
Parkinsons
General: What is the Dorsal pathway?
arousal system sends axons to thalamus–> synapse–> axons from thalamus to cortex
non-specific nuclei of thalamus
neurons with EAA input interact with a series of intracortical neurons that release GABA to create oscillations that are seen in EEG
General: What is the Ventral pathway?
arousal system sends axons straight to cortex–> synapse directly onto cortical neurons
What is the function of all arousal systems?
- RAS/parabachial EAA system crucial for increasing general excitability of cortical neurons
- Cholinergic system adds to that general excitation
- NA and 5-HT systems move us from being awake to being more generaly aware of incoming information
- DA systems adds to that awareness asociated, particularly focused awareness associated with novel stimuli; role not well defined
What is the neuronal loss in a persistent vegetative state?
in persistent vegetative state, rostral regions of pons/midbrain/thalamus show neuronal loss that exceeds that of cortex (cortical neurons are 10-30 mV hyperpolarized relative to their threshold
What is hit hard in Alzheimer’s disease?
cholinergic systems!!
mental processes slow dramatically and memory formation profoundly impaired
What does the alerting response in the EEG an indicator for? when does this occur?
cortex is looking for or expecting sensory input ; more AWARE now
when NA and 5-HT systems active
What possible treatment has produced dramatic increases in cognitive function in some patients with a persistent vegetative state?
Levadopa
what happens during sleep?
what does that do to the cortex?
thalamocortical neurons are hyperpolarized and show occasional bursts (spindle-like discharges)
the hyperpolarization essentially cuts cortex off from excitatory influence during deepest levels of sleep, so not releasing EAA
basically: thalamus and cortex disconnected; last thing to come through is auditory
