Investigating the neural ensembles underlying the encoding of memory in zebrafish

Investigating the neural ensembles underlying the encoding of memory in zebrafish

How animals respond to their environment largely depends on their past experiences. In fact, understanding how these subjective experiences are formed and how they influence behavior is one of the ultimate goals of neuroscience. However, how memories are established in the brain is still poorly understood in mammals and even less in primitive vertebrates. Although the formation of memory has been largely studied at the single-neuron level, more recent studies have shown that the establishment of memory traces necessitates the interactions between multiple brain regions including the cortex, amygdala and hippocampus. Yet, imaging across these vast brain areas is very challenging in mammals due the complexity and size of the mammalian brain. Since there are accumulating evidence illustrating that the hippocampus and amygdala are evolutionary conserved across vertebrates, here, I will use an optically transparent and genetically amenable vertebrate model that allows for brain-wide imaging of neural activity: the juvenile zebrafish. First, I will use electrophysiological and immunochemical methods to identify the major neuronal populations in the fish’s hippocampal homologue (WP1). Next, I will use a combination of electrophysiological recordings and whole-brain two-photon calcium imaging to investigate the connectivity architecture and synaptic organization of the neural ensembles of the hippocampal homologue in zebrafish brain explants (WP2). Finally, I will characterize what kind of information does the hippocampal homologue encode during learning and how does the brain-wide neural activity changes over the course of learning in behaving animals (WP3). Collectively, this project will identify, for the first time, key fundamental neural mechanisms that underlie memory formation across vertebrates and will provide a basis for future projects seeking to study complex neural computations in primitive species.