Brain Arousal Systems (Karius) Flashcards
Components of consciousness:
Arousal (being awake)
Awareness (being actually aware)
Brain injury can dissociate these components
Coma:
Vegetative state:
Minimally conscious state:
- neither awake nor aware
- Has sleep/wake cycles but no evidence of awareness
- clear sleep/wake cycles, reproducible awareness by ability to respond to simple commands, limited or absent communication
Most people in coma or vegetative state show ….
How do cortical neurons behave in these patients?
Damage to lower levels of the brain (midbrain, brainstem and hypothalamus). Used to be thought that to lose awareness means damage to the cortex.
-Cortex neurons are usually alive, but hyperpolarized (not firing), about 30 mV below threshold. Signals not strong enough to generate AP.
What does the hierarchy of consciousness suggest about its physiological basis?
Different levels (coma, vegetative etc.) are a result of different levels of cortical excitation
Cortex and consciousness
Cortex cannot excite itself. It relies on ascending signals to get activation.
Brainstem arousal systems:
5 neurotransmitter systems
Excitatory amino acid system Cholinergic system Norepinephrine Serotonin Dopamine
Excitatory amino acid system:
Core of the arousal systems
Associated with RAS within the medulla
Arise from parabrachial nuclei in the rostral pons
Cholinergic system:
What nuclei?
Ach and EAA are critical for producing arousal
Associated with pedunculopontine tegmental and laterodorsal tegmental nuclei
Norepinephrine system:
What nuclei?
Associated with locus ceruleus
Moves us from arousal to awareness (along with serotonin)
Serotonin system:
What nuclei?
Associated with midline raphe nuclei
Moves us from arousal to awareness (alogn with Norepi)
Dopamine system:
What nuclei?
Associated with ventral tegmental area
Moves us from awareness to focused alertness
Which systems are required to get from Coma to vegetative state?
Excitatory amino acids
Acetylcholine
Excitatory amino acids:
RAS (reticular activating system)
Where is it?
What type of input does it receive?
- Mid ventral portion of the medulla and midbrain
- Receives all ascending sensory and trigeminal tracts, auditory and visual info
Characteristics of RAS input
Synapses converge. modal specificity is lost since there are so many sensory inputs coming in. We know there is some sensory input but don’t know what kind specifically. Not part of processing (does not tell you what you’re feeling etc.), but tells you there’s some input there.
Describe the dorsal pathway from RAS:
Axons from the RAS go to thalamus > synapse at non-specific nuclei in the thalamus
EAA/glutamate released in the thalamus > diffuse pathways to all higher levels (sends neurons broadly over the cortex)
Describe the ventral pathway from RAS:
Nonspecific pathway and bypasses the thalamus > basal forebrain and hypothalamus > diffuse pathways to all higher levels (sends neurons broadly over the cortex)
Parabrachial nuclei:
What areas of the brain?
Mostly the lateral subnucleus, but also medial and intermediate nucleus
Sensory info comes in similar to how it comes in via RAS (all sensory modalities, modal specificity is also lost)
RAS vs parabrachial nuclei?
Parabrachial travels only on ventral pathway which bypasses the thalamus and synapses to the hypothalamus instead
Both use EAA/glutamate
Role of the EAA/glutamatergic pathways:
Core of the arousal pathways
Provides baseline excitation of the cortex that is necessary to producing arousal
This is NOT sufficient to produce awareness
Which system is crucial in getting from coma to vegetative state?
Which nuclei do these neurons originate from?
What neurotransmitter is important for the cholinergic system?
Cholinergic arousal system (needs EAA to be working too)
Pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei
Acetylcholine (duH)
Inputs to the PPT/LDT…
Output pathways…
Similar to RAS. All afferents send info here and modal specificity is also lost
Uses both ventral and dorsal pathways just like RAS
What disease damages the cholinergic system?
Alzheimer’s
Function of the Cholinergic arousal system:
Also provide baseline excitation to the cortex. Necessary but NOT sufficient for arousal
Damage to the cholinergic arousal system
Damage to the PPT/LDT nuclei result in cognitive deficits that slow cortical processes (e.g. resulting in Alzheimer’s memory loss since it requires repetitive activation of the memory circuits)
Importance of EAA and cholinergic inputs
Ach and EAA systems need to function to establish arousal and sleep/wake cycles
Core: EAA via the RAS/parabrachial nuclei
Helpers: Ach via the PPT/LDT
Which systems are critical for moving from persistent vegetative state to awareness?
Noradrenergic and serotonergic systems (lower systems need to be working as well)
Where are the neurons producing Norepinephrine found?
Locus ceruleus in the pons
Norepinephrine system receives input from ….
- Paragigantocellularis nuclei in the brainstem.
- Perifascicular area of the nucleus prepositus hypoglossi (PrH)
- PAG (periaqueductal grey) in the caudal midbrain - important for controlling pain inputs
- higher structures (hypothalamus, amygdala, cortex)
What kind of input is received by the LC?
Different from the RAS/PPT. Somewhat processed, a bit more specific than what the RAS/PPT/LDT are receiving
Outputs from the LC:
Axons from LC join axons from RAS/Parabrachial/PPT/LDT in the dorsal and ventral pathways Ascending bundle (dorsal noradrenergic bundle) sends info to higher brain (except the striatum)
Function of the Norepinephrine system:
Startle/altering response on the EEG
Sleep/wake cycle
Behavioral vigilance (active when paying attention to something)
Where are the cell bodies located for the serotonergic arousal system?
Midline raphe nuclei
What inputs go to the serotonergic system:
Sensory from the spinal cord especially sensory info from trigeminal sensory nuclei, periaqueductal gray (pain control)
5HT outputs travel through…
Ventral pathway mostly, but also dorsal pathway
Function of the serotonergic system:
Produces "quite awareness" of surroundings Pain modulation Circadian rhythm Energy balance/food intake Mood and affect
What are the roles of Norepinephrine and Serotonin in arousal systems?
NE specifically gets us to “awake” state
Both seem to be important in getting us from “awake” to “aware”
What system is crucial for focused attention/alertness?
Dopaminergic systems
Pathway to alertness is unclear
Where are dopaminergic neurons located?
Ventral Tegmental Area (VTA)
Functions of the dopaminergic pathway:
- Alertness in response to novel stimuli (agonists can improve cognitive function in vegetative patients). Dopamine is essential for alertness
- Also has role in motor control and emotion
How does the dorsal pathway work?
Arousal system nuclei send axons to thalamus > synapse at the nonspecific nuclei > thalamo-cortical neurons (excitatory) > releases EAA through diffuse pathways in the cortex
What else do the thalamo-cortical neurons excite?
Intracortical neurons that release GABA. Wave of excitation (EAA) and inhibition (GABA) seen on EEG
How does the ventral pathway work?
Arousal system nuclei > axons to cortex (bypass thalamus) > synapse directly to cortical neurons
Thalamocortical neurons during sleep:
Are in a hyperpolarized state, so sensory input does not have same effect compared to awake. Occasional bursts of action potentials.
Redraw the schematic for arousal systems and awareness states
Ok
