TAKEHARA LAB

Brain and Behaviour Seminar
2024-2025
4 PM, February 10th
Hybrid format, In-person Psychology Lounge
Dr. Caleb Browne
The Centre for Addiction and Mental Health
"Neural mechanisms underlying the development of substance use disorder and relapse vulnerability"
Substance use disorder (SUD) devastates lives and places a significant burden on the healthcare system. Despite its prevalence, effective treatment options remain limited, and the chronically relapsing nature of SUD makes long-term abstinence exceptionally difficult to achieve. This talk will present a series of preclinical studies aimed at deepening our understanding of neural mechanisms that drive the development and maintenance of SUD. First, I will describe a neural substrate within the nucleus accumbens – a crucial hub of the brain’s reward circuit – that enables drugs of abuse to hijack neural function and disrupt naturalistic goal-directed behavior. I will then outline molecular adaptations that support long-lasting relapse vulnerability in a mouse model of opioid use disorder, with a focus on an epigenetic mechanism in the ventral hippocampus – an important interface between memory and motivation. These studies integrate in vivo two-photon calcium imaging, intravenous drug self-administration, RNA sequencing, bioinformatic analyses, and CRISPR-mediated gene regulation, forming a comprehensive pipeline that has enbled us to generate new insights into how drugs of abuse access and disrupt brain circuits and behaviour. Further, our findings offer novel avenues for developing much-needed therapeutic interventions to combat SUD.
4 PM, March 17th
Hybrid format, In-person Psychology Lounge
Dr. Maxwell Shafer
Department of Cell and Systems Biology, The University of Toronto
"Exploring circadian activity patterns and sleep in hyper-diverse cichlid fishes"
Many of the mechanisms that regulate the phase, duration, and structure of sleep are conserved, yet paradoxically, sleep displays remarkable variation both across and within species. Animals can have different chronotypes (‘early-birds’/‘night-owls’) or spend variable amounts of time asleep (2-18 hrs/day). Species can shift the phase of their activity (nocturnal/diurnal), restrict activity to specific periods (dawn/dusk), or lose rhythmicity entirely. We use multiple fish models to study the genomic, cellular, and evolutionary mechanisms of sleep. Using in lab animal tracking, we have recently identified incredible variation in sleep timing and duration across > 60 species of African cichlid fish from Lake Tanganyika. The diversity observed in these cichlids (10 my of evolution) is equivalent to that seen across all animals, and genome-wide association analysis have identified potential molecular and genetic mechanisms underlying the evolution of nocturnality/diurnality and sleep. Currently in the lab we are following up on these studies, and furthering our exploration of sleep in these fishes. Using hidden markov models we are exploring diversity in sleep states (deep sleep vs light sleep) across species and hope to identify genetic correlates for sleep consolidation and bout structure. Finally, I will also discuss the relationship between environmental factors and social context on the regulation and timing of sleep and activity patterns in shell-dwelling cichlid species. These species live and breed in close association with empty snail shells, and many have highly complex social structures. We have recently identified that both environmental and social cues control activity and sleep patterns in these species, if these factors are missing, individuals switch to nocturnal activity. Based on these studies, we believe that cichlids represent an ideal model clade for studying the evolution and neurobiology of sleep.
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