David Heister (MD/PhD student)

dheister@uams.edu

            REM sleep in the human declines from about 50% of total sleep time (~8 hours) in the newborn to about 15% of total sleep time (~1 hour) in the adult, and this decrease takes place mainly between birth and the end of puberty.  We hypothesize that, if this developmental decrease in REM sleep drive does not occur, lifelong increases in REM sleep drive may ensue, leading to disorders manifesting hypervigilance such as schizophrenia, anxiety disorder and depression.  In the rat, the developmental decrease in REM sleep occurs between 10 and 30 days after birth, declining from over 70% of total sleep time in the newborn to the adult level of about 15% of sleep time during this period.  Phasic activation of a specific group of neurons in the region of the SubCoeruleus nucleus (SubC) in the pontine tegmentum generate a prominent field potential, ponto-geniculo-occipital (PGO) waves, prior to the onset and throughout REM sleep.  The rat does not have a geniculate component and its waveform is called the P-wave.  P-waves occur as singlets and as clusters (3-5 waves/burst) at a frequency of 30-60 spikes/min during REM sleep, generating high frequency (>100Hz) bursts about 25-30 msec before each P-wave.

            I have been recording from SubC cells, which show characteristic spikelets indicative of the presence of neuronal gap junctions.  Note the small potentials in between action potentials in the cell in the figure above.  The presence of gap junctions in the SubC would allow this region to generate synchronized volleys, accounting for the presence of P-waves, a basic manifestation of REM sleep.  The importance of the mechanism being studied should not be underestimated.  The role of REM sleep in development has been linked to the establishment of connectivity, and in the mature brain, to sleep-dependent memory processing.  Dysregulation of the expression of gap junctions in this region could result in major disturbances in connectivity, arousal mechanisms and memory processing.  Once these studies on intact animals have provided baseline observations, animal models of the disorders mentioned can be assessed for differences in gap junction function in the SubC.  Should these reveal differences in gap junction expression, novel, perhaps preventive, therapies may be designed for disorders characterized by increased REM sleep drive.

Sharp electrode recordings of SubC cells.  A.  Spiking pattern of a 12 day SubC cell exhibiting spontaneous action potentials and spikelets.  B.  Superimposed recordings of a spikelet and an action potential shown at the same time scale, but with different amplitude scales.  Note the similar rise time between action potential and spikelet.  C.  Recordings from another SubC cell (9 days) at resting membrane potential (-71 mV) without spontaneous spikelets.  D.  Recording 3.5 min after beginning of superfusion with CAR (40 uM) showing induction of spikelets without changing the membrane potential.  E.  Depolarization to -69 mV induced by 5 min after the beginning of CAR superfusion showing depolarization along with action potentials and spikelets.  F.  Washout of CAR showing return towards resting membrane potential, lack of action potentials and decrease in spikelet frequency.