The Cellular Logic of Sensory Circuits
Perhaps the two most compelling features of the brain are its complex interconnectivity within and between the different parts of the brain, and the myriad types of cell needed to carry out everything the brain is capable of. Our lab is dedicated to mapping the connections within and across these two features—the ways that different classes of cells and the systems they form work together. We believe that only with a quantitative understanding of the heterogeneity of both connectivity and cellular / functional composition, will we be able to elucidate key principles underlying the design and operation of both the healthy and the diseased brain.
We employ a variety of technical approaches, some of which are multidisciplinary and/or were developed in our lab. These include 3D electron microscopic analysis, in vitro and in vivo single and multi-cell targeted recordings, whole-brain connectivity mapping of recorded cells, optogenetics, modelling, and behaviour. Our lab works almost exclusively on mice, which offer a tractable experimental system for establishing causal relationships between the functional connectivity of mammalian neuronal circuits and behaviour.
One critical problem that the brain must solve involves the translation of information between allocentric (world-centred) and egocentric (e.g. head-centred) reference frames; that is, the brain must be able to discern which elements of (for example) sight come from movement in the outside world and which come from movements of the eyes, head and body. Due to the retrosplenial (RSP) cortex's anatomical connectivity with structures such as the hippocampal formation and post subiculum, its involvement in spatial memory retrieval and the fact that it contains cells which code for an animal’s speed, location, and the direction and angular velocity of the head, the RSP is believed to play a fundamental role in solving this problem. Our lab has recently discovered a novel circuit that conveys head motion information from the RSP to the deep layers of the primary visual cortex (V1). We hypothesise that this RSP-V1 cortical network is critical for the construction of an egocentric-based visual representation of the environment which may then be relayed back to the RSP for integration with allocentric information. Using viral tracing, and in vivo imaging and physiology, our current work focuses on establishing the functional connectivity of all the key cell types involved in this newly discovered system.
A second question in the lab focuses on in vivo physiological plasticity, which occurs in response to changes in the sensory and social environment. The glomerular circuit of the olfactory bulb is one model system of choice, as local networks can readily be identified and genetically targeted from one mouse to the next. Compared to the cortex, the glomerulus is anatomically and functionally relatively simple; its cellular composition is well understood. However, the intrinsic properties of glomerular neurons vary according to the glomerulus in which they receive odour input. This intrinsic biophysical diversity is known to depend on the identity of the receptor neurons that relay sensory information to the glomerulus. We therefore use this system to investigate the functional significance of intrinsic diversity and plasticity in the context of olfactory information and learning in the behaving animal.
Brain cellular diversity and connectivity as depicted by Brodmann