Normal sleep

Slow wave sleep:  This is the initial sleep represented by high amplitude slow waves on the EEG (as opposed to the low amplitude fast waves seen in awake patients).  There is normal resting muscle tone in this stage, and the heart and respiratory rates are decreased. 

Paradoxical (REM) sleep:  This follows slow wave sleep in cycles and is represented by low amplitude fast waves that are similar to the wakeful state).  There is flaccid muscle tone (aside from diaphragm function) allowing for paralysis during the dream state.  Sometimes muscle groups will break through the inhibition to cause eyeball movements, facial twitching, or limb jerks.  Respirations are also more shallow and rapid. 

When the neurons in the locus ceruleus and dorsal raphae nucleus are inactive, the pontomedullary centers are released from inhibition and atonia results by Ach release and GSE-LMN inhibition. 

Also inhibition of thalamic neurons (that normally stimulate the cerebral cortex) cause low amplitude fast waves in REM sleep. 

Paradoxical sleep is mediated by a balance of cholinergic inhibition and monoamine suppression. 

Physostigmine and arecoline facilitate REM sleep.

Atropine and scopolamine suppress REM sleep.

Norepinephrine and serotonin also suppress REM sleep. 

*Dobies with narcopesy have been shown to have decreased serotonin, dopamine, and nor-epinephrine and a higher concentration of choloinergic brainstem receptors (so greater cholinergic sensitivity).  Prazosin exacerbates cataplexy.  Alpha1 agonists, alpha 2 antagonists, and D2 antagonists suppress cataplexy. 

Normal waking

Light stimulates the retinal neurons which pass information along the optic nerve to stimulate neurons in the suprachiasmic nucleus in the rostral ventral hypothalamus.  Axons from this nucleus end in a ventrolateral hypothalamic nucleus.  The neurons in this area project to the prosencephalon and brainstem and release hypocretin (orexin).  Hypocretin is a neurotransmitter that stimulates appetite and wakefulness. 

Receptors for hypocretin stimulate release of norepinephrine in the locus ceruleus and serotonin in the dorsal raphae nucleus.  Both of these are inhibitory in the pontine reticular formation.  These RF neurons normally inhibit GSE-LMNs by releasing acetylcholine.  Therefore, inhibition of these inhibitory neurons leads to activation of the GSE-LMNs. 

Narcolepsy

1. Excessive sleepiness
2. Cataplexy
3. Hypnagogic hallucinations
4. Sleep paralysis

Narcolepsy is the abrupt onset of REM sleep without the preceding slow wave sleep.  These patients are often sleepy between sleep episodes.  Cataplexy involves abrupt limb paralysis and collapse. 

Cataplexy has an autosomal recessive inherited basis (canarc gene on chromosome 12, coding for the hypocretin receptor) in Dobermans, Labradors, and dachshunds.  Hypocretin levels are normal in these dogs. 

There may also be an inherited basis in Shetland ponies, miniature horses, and miniature poodles with sporadic cases in several other breeds. 

In acquired narcolepsy, there is a decrease in CSF hypocretin.  This is associated with atrophy of the ventrolateral hypothalamic nucleus. 

Provocative testing:

Food trial (10 bits of food spaces 3 feet apart):  Normal dogs eat all the pieces in less than a minute.  Affected dogs may take 2 minutes or more.

Physostigmine: enhances cholinergic suppression.  Will not affect a normal dog but can elicit a collapse episode in a predisposed dog. 

Preventative testing:

Imipramine enhances monoamine levels/ function and is an anticholinergic to increase wakefulness. 

Atropine reduces cholinergic function to reduce tendency toward cataplexy. 

Therapy:

Imipramine

Methyphenidate

Selegeline

Yohimbine

Veterinary Neuroanatomy and Clinical Neurology, 3^rd edition.  De Lahunta, Glass.  Saunders Elsevier 2009: pp 468-471.