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An intrinsic function of the cholinergic arm of the
reticular activating system (RAS), the pedunculopontine nucleus (PPN), is its
participation in "fight vs flight" responses such that alerting stimuli
simultaneously activate higher thalamocortical (THAL, CORTEX) systems, as well
as postural and locomotor systems (RF reticular formation, SC spinal cord), in
order to enable an appropriate response. The P50 midlatency auditory-evoked
potential appears to be an ascending manifestation of the cholinergic arm of the
RAS in eliciting changes in arousal state in thalamo-cortical structures.
Abnormalities in the manifestation of the P50 potential are present in disorders
that include: 1) dysregulation of sleep-wake cycles; 2) abnormalities in
reflex/postural, especially, startle and blink responses; and 3) malfunctions in
flight vs flight responses. In general, the P50 potential appears to be
upregulated (increased amplitude and/or decreased habituation) in disorders that
are marked by upregulation of RAS outputs (hypervigilance), and downregulated in
disorders characterized by decreased RAS outputs (hypovigilance). Many of the
disorders discussed have a developmental etiology and a postpubertal age of
onset, e.g. schizophrenia, anxiety disorders, depression. We have developed the
rodent equivalent of the P50 potential, the rat P13 potential, which has the
same characteristics of a) sleep state-dependence (present during waking and REM
sleep, absent during slow wave sleep), b) mediated by cholinergic projections
(blocked by muscarinic antagonist scopolamine) and c) rapid habituation
(generated by multi-synaptic, low security "reticular" pathways). The figure
below shows how the two waves occur during the inhibition of the electromyogram
of the blink reflex (BR) or the startle response (SR).
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