what really happens in the scn at night
TRANSCRIPT
Journal of Physiology (2001), 532.1 1
What really happens in theSCN at night
R. E. J. Dyball and K. Saeb-Parsy
Department of Anatomy, University ofCambridge, Cambridge CB2 3DY, UK
It is generally believed and clearly stated inmost text books of physiology that the cells inthe suprachiasmatic nucleus (SCN) of thehypothalamus show a daily variation in theiractivity and that this is reflected by changesin the spike frequency that can be recordedfrom the nucleus. Inouye & Kawamura (1979)showed that multiple unit activity recordedfrom hypothalamic islands increased duringthe time of day that the animals would havebeen inactive. A similar rhythm was reportedin the activity of cells acutely dissociatedfrom the suprachiasmatic nucleus (Welch et al.1995) and in intact animals Meier et al. 1998).These studies are, however, incomplete in tworespects; first, there is no analysis of theactivity either to show that it is rhythmic inthe statistically rigorous sense or to define andplace confidence limits on the timing of thepeaks and troughs of the activity. A newpaper by Pennartz and colleagues in this issueof The Journal of Physiology does not addressthis issue but represents a great leap forwardin another direction. They have shown, usingrigorous whole-cell recording techniques, thatalthough the number of cells in the SCN whichrespond to optic nerve stimulation staysconstant, there is a difference in the post-stimulus whole-cell membrane current evokedby optic nerve stimulation at different timesof day. During the day, the current mediated
by the NMDA component of the EPSC inrandomly selected cells in the SCN was foundless frequently than it was during the nightand when it was encountered, its magnitudewas significantly smaller in amplitude (seeFig. 1). It is thus likely that despite itsrelatively low amplitude and slow timecourse, the NMDA receptor-mediated EPSCmight exert a physiological role in modulatingthe retinal input to the SCN and thuscontrolling the activity of the cells whichrepresent the circadian oscillator.
This finding represents an important additionto our understanding of the daily modulationof the activity of the SCN. A great deal isknown of the neurochemical changes whichoccur in the nucleus at different times of day(see e.g. Inouye & Shibata, 1994). Much recentwork on circadian biology in mammals hasbeen directed to determining the interrelationbetween the mouse equivalents (mPer 1, 2 and3) of the Drosophila clock gene period (per)and the regulation of their activation by theprotein products of another gene, Bmal1,leading to peaks in mPer1 transcription in theday and peaks of Bmal1 transcription at night(see e.g. Dunlap, 1999). Such changes alone donot affect either the activity of the SCN cellsor their output. To affect the other regions ofthe CNS to which SCN cells project, changes ingene transcription must modulate spikeintervals. Spike interval coding determinesthe release of transmitter from axon terminalsand this in turn must depend on channelactivity and membrane currents. The paperby Pennartz et al. (2001), while it does notestablish a direct connection between, forexample, the peak in Bmal1 transcription
that occurs at night and the expression of therelevant receptor protein, is the first thatcharacterises an important change in theactivity of a specific receptor protein. Suchchanges almost certainly underpin the changeswhich are known to occur in the activity ofthe nucleus. It implies that the properties of agiven neural pathway in the CNS are notnecessarily constant at different times in thelight–dark cycle. Thus neural connections arenot all hard wired but change quite rapidlywith time. Synaptic plasticity (at least insome situations) thus appears to arise fromdaily alterations in postsynaptic receptorexpression. As time goes on we expect to seeother reports of associated changes in theactivity of different cell surface proteins.
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Figure 1
Diagram to illustrate that, during the day,the SCN cells show only a short-durationcurrent in response to optic nervestimulation (long thin arrow). During thenight, however, an additional currentblocked by AP5 can also be detected (shortbroad arrow).