The balance between excitation and inhibition is essential for the proper function of neuronal networks in the brain. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) contributes to the network dynamics within the suprachiasmatic nucleus (SCN), which is involved in seasonal encoding. We investigated GABAergic activity and observed mainly inhibitory action in SCN neurons of mice exposed to a short-day photoperiod. Remarkably, the GABAergic activity in a long-day photoperiod shifts from inhibition toward excitation. The mechanistic basis for this appears to be a change in the equilibrium potential of GABA-evoked current. These results emphasize that environmental conditions can have substantial effects on the function of a key neurotransmitter in the central nervous system.S easonal changes in the photoperiod of the Earth's temperate zones affect the behavior and physiology of many organisms (1). The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, can adapt to changes in day length and displays a compressed circadian pattern of electrical activity in short winter days and a decompressed pattern in long summer days (2). This pattern is based on a change in the phase distribution of the activity patterns of individual neurons, which becomes broad in the summer and narrow in the winter (3). The mechanisms that mediate and regulate photoperiod-induced phase distributions are currently not known.The neurotransmitter γ-aminobutyric acid (GABA) is believed to be involved in the phase adjustment and synchronization of the SCN neuronal network (4, 5). GABA and its receptors are expressed in most SCN neurons (6). GABAergic inhibition has been indicated to be important in normal physiological function within the brain. Alterations in this system (i.e., less inhibition) are shown to cause neurological disorders, such as epilepsy and autism (7,8). In addition to its classical inhibitory function within the SCN network, GABA has more recently been shown to also act as an excitatory transmitter, although its exact role is uncertain (4, 9-13). To understand the influence of photoperiod on GABAergic function, we studied synaptic activity, using patch clamp, and GABAergic responses, using Ca 2+ imaging techniques, in the SCN of mice adjusted to long-day and short-day photoperiods. We hypothesized that the narrow, synchronized phase distribution of active neurons during short-day photoperiods would result in increased synaptic activity during the day. Surprisingly, however, exposure to a short-day photoperiod decreased the frequency of spontaneous GABAergic synaptic events compared with the long-day photoperiod.Subsequently, we tested the effect of photoperiod on GABAinduced excitation in the SCN neuronal network. Ca 2+ transients were measured in response to GABA stimulation in long-day and short-day photoperiods. Interestingly, of all cells from the long-day photoperiod, 40% were excitatory and 36% were inhibitory. In contrast, in the short-day photoperiod, 28% of the c...