A conserved circadian clock provides the temporal framework for rhythmic behaviour and metabolism across the phylla, and is regulated or entrained by environmental factors such as light and temperature, known as zeitgebers (ZT). In flies, entrainment to light is mediated by the blue-light sensitive protein CRYPTOCHROME (CRY). When activated it is able to interact with core clock components to ensure the molecular clock is optimised to the light-dark cycle, as well as many other proteins involved in various physiological processes such as magnetoception, courtship behaviour and metabolism. This project investigates the role of CRY in the regulation of neuronal excitability in a specific subset of neurons of the Drosophila CNS called the large ventral lateral neurons (l-LNvs). Overexpression of a constitutively active form of CRY (CRYΔ) is used to study the role of CRY within the circuitry involved in circadian clock regulation. Whole cell patch clamp recordings of l-LNvs in whole brain preparations of adult Drosophila were performed (Multiclamp 700B, pClamp 10, Axon Instruments). Female flies w1118 /UAS cryΔ72.3; tim-GAL4/ UAS GFP co-expressed CRYΔ and GFP in clock cells, including the l-LNvs. w1118 /+; tim-GAL4/ UAS GFP females were used as controls. Recordings were conducted during ZT10-12 to eliminate any changes in the activity seen in the l-LNvs due to a circadian effect. Larval foraging activities were measured as crawling distance in 10min (ANYmaze) using female larvae that were w1118; elav_GAL4/+; UAS-cryΔ4.1/+ and compared to w1118; elav_GAL4/+; +/+ for control. Data are expressed as mean ±SEM (n). Statistical analyses were carried out using standard unpaired t-test, * indicates p<0.05. Electrophysiological recordings revealed that overexpression of CRYΔ in l-LNvs induces increased outward currents at 0mV from 167 ±8pA (3) to 234 ±20pA* (3) and at -10mV from 79 ±4pA (3) to 124 ±17pA* (3). Investigations of the spontaneous action potential (AP) firing frequencies were also conducted but have thus far not shown a significant difference, although there is a trend of increased AP firing rates in response to current injection. Larval foraging assays to investigate the motor effects of CRYΔ overexpression at the larval neuromuscular junction (NMJ) have shown an increase in the distance travelled by CRYΔ expressing larvae from 0.5 m (14) to 0.67 ±0.04 m* (17). This data indicates that CRYΔ expression is able to mediate changes in activity at the NMJ as well as in CNS clock cells. Further CNS recordings are needed to allow firm conclusions from the electrophysiological data collected so far.