Neuropsychiatric and neurodevelopmental diseases manifest through clinical symptoms that result from abnormal functioning of specific brain circuits. Significant advancements have been achieved in comprehending the specific brain regions implicated and the chemical mechanisms accountable for these disorders. Nevertheless, the primary obstacle in developingnovel treatments is the constrained utility of behavioral animal models. While alterations in behavior may suggest an enhancement in the clinical phenotype, they may not necessarily represent an improvement in the fundamental circuitry. However, theycould be attributed to unrelated structural modifications. In addition, although preclinical models serve as valuable tools for research, their capacity to accurately forecast results in humans is frequently uncertain, posing a substantial challenge to theadvancement of drugs. The recent advancements in electrophysiology1 have made it possible to monitor the activity of individual neurons on a wide scale and with great precision in freely moving mice andopenup the opportunity to find patterns of neural activity in situations that cause diseases. We consistently record from more than 250 neurons simultaneously over numerous days using a single Neuropixel 2.0 probe2 implanted using lightweight 3D-printed fixtures3. We administered Dizolcilpine (MK-801), a potential medication that acts as an uncompetitive antagonist of the N-Methyl-D-aspartate (NDMA) receptor4. We assessed the temporal modulation of neuronal activity by administering varying doses of MK-801. We discovered substantial disparities between the control group and each group that received different concentrations, regardless of animal behavior. Subsequently, we inquired about the feasibility of using only electrophysiological footprints to forecast the administered concentration of dizocilpine. We employed temporal variations in the spike statistics of individual neurons and built
multiclass classifier. Subsequently, we accurately forecasted the concentration of the supplied medication to be above 70%. In conclusion, our existing platform paves the way for advancements in drug development and personalized treatment.

Neuroimaging has been a powerful method to measure activity of neural circuits. Technological and genetic advances now allow us to observe neural circuits during behavior in brain-wide networks. Dr Ayaz will introduce several of these approaches imaging neural circuits across scales and powerful optogenetic tools used for the manipulation of specific neural circuits in vivo. The presentation will also cover the potential use of these approaches in deciphering circuit function anomalies in in vivo models of brain disorders.

Discussions and contributions from guest scientists (Details will be announced)