Using techniques that allow us to probe brain function from single synapses to awake, behaving animals, our goal is to understand how physiological and psychological challenges lead to long-term changes in the brain. We focus on neurons in the hypothalamus that coordinate the mammalian response to stress, with a particular interest in how the molecules, or neuromodulators released at the onset of a stress leave a lasting imprint to alter subsequent stress responses.
These cells are at the apex of the hypothalamic-pituitary axis. Dysfunction of the HPA has been implicated in a number of mental health disorders, including depression, anxiety and post-traumatic stress disorder. Consequently a better understanding of the mechanisms that control and modify the activity of hypothalamic command neurons is critical for designing rational therapeutic approaches for these disorders.
We are interested in understanding the synaptic correlates of behavioural challenges such as restraint stress and physiological challenges such as changes in fluid volume. We are currently focusing on long-lasting changes in the efficacy of both glutamatergic and GABAergic synapses that regulate the output of neuroendocrine cells in the paraventricular nucleus of the hypothalamus.
We have ongoing investigations into the role of glial cells in regulating synaptic function. In particular, we are pursuing the molecular mechanisms underlying the release of ATP from glia and also conducting experiments to better understand how glia are recruited following synaptic or neural activity.
How do we answer these questions?
We use: patch clamp recordings from neurons in brain slices for the measurement of excitatory and inhibitory synaptic currents; optogenetics for stimulating specific neural pathways in vivo and in vitro; UV laser uncaging of bioactive molecules; immunohistochemistry for the labeling of receptors and neuronal subpopulations; in vivo microinjection; behavioural manipulations and hormone assays.