Cameron Good goodcameron@uams.edu

There is a dramatic decrease in the amount of REM sleep in humans from birth through puberty, beginning with 8 hours in the newborn and declining to around 1 hour in the adult.  If this natural decrease does not occur, then a lifelong increase in REM sleep may ensue that could lead to such symptoms as hypervigilance, exaggerated startle responses and even hallucinations.  The pedunculopntine nucleus (PPN), as the cholinergic arm of the reticular activating system (RAS), is the main nucleus in the brainstem responsible for controlling our level of arousal and changes in sleep/wake state, which is why it is crucial for us to understand at a cellular level the mechanisms driving this natural decrease in REM sleep.  The decrease in REM sleep drive in the rat occurs between 10 and 30 days postnatally, the greatest decrease between 12 and 21 days.  Our findings suggest a dramatic change in cholinergic, especially nicotinic, inputs to the PPN take place during this period.

The top recording below shows a direct response of a PPN neuron to micropressure application of DMPP in the presence of TTX.  This shows that there is direct hyperpolarization of this PPN cell's membrane by the nicotinic agonist DMPP.  The second recording shows application of DMPP, but the response was blocked by pre-treatment with the nicotinic receptor blocker mecamylamine (MEC), indicating that the response is purely (a4) nicotinic in nature.  The recordings on the right show this cell’s responses to intracellular current injection from -0.5 to +0.2nA.  These results demonstrate a potential novel site of action for nicotine, and may help explain why 1) nicotine has anxiolytic effects (it may inhibit RAS output) and 2) patients with schizophrenia, anxiety disorders and depression all smoke more than the general smoking population.  Since the PPN is responsible for our level of arousal, these patients may be undertaking a form of self-medication in an attempt to calm down.  My project will focus on how this response changes across the developmental decrease in REM sleep.

Exposure to smoke during pregnancy or soon after birth may affect the normal development of PPN neurons, which could have long-term consequences for sleep-wake and arousal control.  Dysregulation of this system may underlie the reported attentional and cognitive deficits evident in children exposed to smoke before birth and early in life.