Synaptic inhibition: its role in suprachiasmatic nucleus neuronal thermosensitivity and temperature compensation in the rat

Whole-cell patch clamp recordings of neurones in the suprachiasmatic nucleus (SCN) from rat brain slices were analysed for changes in spontaneous synaptic activity during changes in temperature. While recent studies have identified temperature-sensitive responses in some SCN neurones, it is not known whether or how thermal information can be communicated through SCN neural networks, particularly since biological clocks such as the SCN are assumed to be temperature compensated. Synaptic activity was predominantly inhibitory and mediated through GABAA receptor activation. Spontaneous inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were usually blocked with perifusion of 10–50 μm bicuculline methiodide (BMI). BMI was used to test hypotheses that inhibitory synapses are capable of either enhancing or suppressing the thermosensitivity of SCN neurones. Temperature had opposite effects on the amplitude of IPSPs and IPSCs. Warming decreased IPSP amplitude but increased IPSC amplitude. This suggests that thermally induced changes in IPSP amplitude are primarily influenced by resistance changes in the postsynaptic membrane. The thermal effect on IPSP amplitude contributed to an enhancement of thermosensitivity in some neurones. In many SCN neurones, temperature affected the frequency of IPSPs and IPSCs. An increase in IPSP frequency with warming and a decrease in frequency during cooling made several SCN neurones temperature insensitive, allowing these neurones to maintain a relatively constant firing rate during changes in temperature. This temperature-adjusted change in synaptic frequency provides a mechanism of temperature compensation in the rat SCN. Mammalian circadian rhythms are known to be generated by the suprachiasmatic nucleus (SCN) in the ventral hypothalamus. It is generally accepted that all biological clocks, such as the SCN, exhibit temperature compensation (Pittendrigh, 1993), where adjustments to changes in temperature maintain a constant rhythm period near 24 h. Without this ability, uncompensated clocks would be poor timekeepers, generating longer or shorter biological rhythms with changes in body temperature. For homeothermic animals, body temperature is regulated within a narrow temperature range. It is, therefore, unclear whether the mammalian SCN exhibits temperature compensation or whether this nucleus is ‘temperature protected’ by homeostatic thermoregulatory responses controlled by the preoptic and anterior hypothalamic area (PO-AH) (Boulant, 1996). For rats, normal body temperature averages 37°C and exhibits a circadian rhythm that oscillates by ±1°C over the course of a 24 h day (Satinoff et al. 1982). In these animals, however, core temperature can quickly rise by as much as 2°C due to handling stress, fever, or exposure to a novel environment (Kluger, 1991). Therefore, even mammalian SCN neurones are susceptible to changes in core temperature beyond the boundaries of normal circadian oscillation. Numerous studies have examined the inherent and synaptic temperature-sensitive properties of neurones in the PO-AH (Hori, 1991; Boulant, 1996). Recent evidence indicates that synaptic inhibition can increase neuronal thermosensitivity, since cooling increases the size of inhibitory postsynaptic potentials (IPSPs) and enhances their inhibitory ability to slow down firing rate (Curras et al. 1991). Few investigations have examined the influence of temperature on SCN neuronal activity. Extracellular studies identified the presence of temperature-sensitive neurones in the SCN (Derambure & Boulant, 1994; Miller et al. 1994), but it is not known whether these thermal responses are inherent or synaptically generated. In addition, no investigations have identified a temperature-compensatory mechanism within the SCN, but it has been presumed that synaptic inhibition could play a role in dampening SCN neuronal responses to stimuli such as temperature (van den Pol, 1991; Strecker et al. 1997). Synaptic inhibition in the SCN is widespread, well documented, and known to be primarily mediated through GABAA receptor activation (Decavel & van den Pol, 1990; Liou & Albers, 1990; van den Pol, 1991; Kim & Dudek, 1992). Synaptic inhibition may actually help to enhance SCN neuronal thermosensitivity, much like the cool-induced enhancement of IPSP size in the PO-AH (Curras et al. 1991). This effect could be an important feedback mechanism for circadian timekeeping of body temperature rhythms. Alternatively, should the frequencies of IPSPs change in relation to temperature, postsynaptic neurones would become less temperature sensitive by receiving more inhibition at higher temperatures and less inhibition at cooler temperatures. This thermally mediated change in IPSP frequency would provide a synaptically generated temperature compensation. The present intracellular study examined the effect of temperature on inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in order to determine the role of synaptic inhibition in SCN neuronal thermosensitivity.