The goal of my lab is to understand how physiological and behavioural challenges lead to long-term changes in neural circuitry in the hypothalamus. We focus on neurons that coordinate an organism's response to stress, with a particular interest in how the molecules released at the onset of a stress leave a lasting imprint to alter subsequent stress responses.

Since the hypothalamic-pituitary axis has been implicated in a number of mental health disorders, including depression, a better understanding of the mechanisms that control the hypothalamic command neurons is critical for designing rational therapeutic approaches to these disorders.

 

What are the questions we ask?

We are currently exploring three lines of investigation:

  • 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.

 

  • We are interested in better understanding the properties of glutamate synapses onto vasopressin neurons. Specifically, we have observed that these synapses exhibit a form of transmitter release that is temporally disconnected from the presynaptic action potential. Ongoing work is examining the contributions of this asynchronous release to information coding in these neuroendocrine cells.

 

What are the techniques we use?

We use a number of experimental techniques to answer the above questions. These include, but are not limited to: patch clamp recordings from neurons in brain slices for the measurement of excitatory and inhibitory synaptic currents; UV laser uncaging of bioactive molecules; immunohistochemistry for the labeling of receptors and neuronal subpopulations; in vivo microinjection; behavioural manipulations and hormone assays.