Figure 1: Expression of the hM4D/CNO pharmacogenetic inhibition tool in cell bodies and projections of the VMH in Nr5a1::hM4D-2A-tomatoF transgenic mice as revealed by farnesylated tomato (red) reporter protein (B. Silva)


Figure 2: Microglia (green cells) visualised in the hippocampus of Cx3cr1GFP transgenic mice (cell nuclei labelled in blue, R. Paolicelli)

The Gross group uses pharmacological, histochemical, electrophysiological and behavioural genetic approaches to study the neural circuits underlying behaviour in mice.

Previous and current research

The laboratory is interested in understanding, at a molecular and neural circuit level, how early life events influence brain development in order to establish behavioural traits in adulthood, with a particular focus on fear and anxiety. We are currently pursuing two areas of research:

Neural circuits encoding fear and anxiety

Fear is a mental state elicited by exposure to threats or cues that signal those threats that is part of our natural defense mechanism. However, in its pathological form fear can become excessive or inappropriate – features associated with anxiety disorders. The amygdala plays a central role in processing threat stimuli that are then integrated by downstream hypothalamic and brainstem circuits to produce appropriate defensive behaviours. Our team has showed that distinct amygdala outputs and downstream circuits are recruited in response to different types of fear with defensive responses to painful stimuli, predators, and bullies mediated by distinct pathways (Gross and Canteras, 2012; Silva et al., 2013; Figure 1). These data suggest that pathological fear comes in different flavours and may be amenable to selective therapeutic treatment. Current work in the lab combines molecular genetic, electrophysiological, and behavioural methods in mice to understand how amygdala, hypothalamic, and brainstem circuits support and adapt fear responses to diverse threats.

Developmental programming of brain wiring by microglia

Microglia are non-neuronal cells of the myeloid lineage that infiltrate the brain during development and are thought to play a role in brain surveillance. Recent studies from our group and others have shown that microglia play a key role in the elimination of synapses during postnatal brain development, a phenomenon called ‘synaptic pruning’ (Paolicelli et al., 2011). Mice with deficient synaptic pruning show weak functional brain connectivity, poor social behaviour, and increased repetitive behaviour – all hallmarks of autism – suggesting that some features of this neurodevelopmental disorder may depend on a deficit in synaptic pruning (Yang, Paolicelli et al., 2014). We are currently using a variety of tools to identify the ‘eat me’ and ‘spare me’ signals that regulate pruning and understand how synapse elimination remodels neural circuits during development.

Future projects and goals

We aim to discover the neural circuits and molecular mechanisms that support individual differences in behavioural traits in health and disease. On the long term, this should allow us to form specific hypotheses about how human behaviour is determined and lead to improved diagnostic and therapeutic tools for mental illness.