Research in the Lab
The overarching research goal in our laboratory is to understand how processing in specific brain circuits works to support natural communication behaviors. We aim to reveal neural mechanisms that allow organisms to detect and recognize familiar individuals, to gather information about their identity and social status, and to select appropriate behaviors.
Mice are capable of acquiring detailed profiles on one another from the smells and sounds experienced during their social encounters. Using imaging, electrophysiological, and molecular techniques, we work to understand the neuronal mechanisms in both primary sensory areas that support these forms of communication and in deeper areas to ascertain how sensory data are collected and integrated into hormonal and electrical signals that promote appropriate behavioral choices.
The scientific benefit of this approach is twofold. First, we want to identify fundamental principles for how the brain controls complex behavior. Second, impairment of social perception and cognition is a core feature of the autism spectrum disorders (ASD). If we can ascertain the neural circuit substrates of social behavior in normal mice, we can make and test predictions for how the circuitry is affected in mouse models of ASD. The results are likely to tell us more about the synaptic modifications that occur in human autism.
Circuits underlying Maternal Behavior
Motherhood and parental experiences trigger dramatic changes in rodent behavior and the underlying neuronal circuitry supporting these behaviors. Many of these changes rely on multi-sensory cues provided by the pups to the parent both during and after parturition. We are interested in how these socially relevant, multi-sensory cues are integrated in the brain. To this end, we study the expression of pup retrieval behavior — a behavior that relies on auditory, olfactory, and somatosensory cues — and the plasticity in cortical and limbic structures that supports the development of this behavior. In both mothers and virgin, surrogate female mice, we combine chronic imaging, electrophysiological, and opto/chemogenetic methods to explore the neuronal circuits involved in pup retrieval and how these circuits change as the animals become proficient with the behavior.
Olfactory Processing in Primary Sensory Circuits
The lab is interested in detailing the neural changes that underlie olfactory communication and the formation of olfactory memories. To this end, we assay activity in the main olfactory bulb (MOB) as animals perform olfactory driven behaviors including recognition and discrimination of the odors of conspecifics.
In particular, we have focused on the activity of olfactory interneurons including granule cells (GCs) that have long been hypothesized to update MOB circuits in accordance with the context in which an animal experiences odors. We have developed loose-patch electrophysiological methods for recording these cells in awake, head-fixed mice, giving us the first glimpse of the dynamics of these cells in behaving animals. Using both in vivo imaging and electrophysiology techniques, we also examine how the activity in GCs and other MOB neurons changes in response to noradrenaline, a neuromodulator particularly implicated in the formation of olfactory driven social memories.
The Role of Noradrenaline in Mouse Social Behaviors
Many social behaviors including mating and maternal care depend on release of the neuromodulator noradrenaline (NA) from the brainstem nucleus locus coeruleus (LC). LC in turn projects widely throughout the brain. However, the dynamics of LC activity during social behavior are not well characterized, and how NA influences neuronal activity and synaptic plasticity in LC target regions is incompletely understood. Our lab works to narrow this gap in understanding through both direct recordings (via multi-channel electrode arrays) and direct opto/chemogenetic manipulations of LC during mouse mating and maternal care behaviors. Furthermore, using imaging and in vivo patch electrophysiology, we explore how NA influences neuronal activity in primary sensory structures in response to socially relevant cues.
Impaired Social Behavior and Neural Circuits in Mouse Models of Rett Syndrome
Patients with Rett syndrome, a neurodevelopmental disease caused by mutations in the MeCP2 gene, display significant social, emotional, and motor deficits. These deficits are thought to manifest through disruptions in neuronal wiring and synaptic plasticity, but linking aberrant circuit wiring to disruptions in behaviour still proves difficult. We have developed a novel method to assay social recognition in a mouse model of Rett that exploits a mouse mother’s auditory recognition of pups’ vocalizations. Using this assay, we have shown that the mutant mice exhibit deficits in communication and learning not unlike those in human patients and have further demonstrated that at least some of these deficits are due to disrupted processing in the auditory cortex. Through a combination of molecular and electrophysiological techniques, we are now exploring how aberrant genetic expression and synaptic plasticity contribute to these disruptions.