A major focus of research in our laboratory is to understand integrative mechanisms by which the brain controls homeostasis. Homeostasis is known to be dependent upon the coordinated activity of two major information-processing systems: the autonomic and the endocrine/neuroendocrine systems. Disruption of homeostasis can lead to various forms of disease states, including hypertension, congestive heart failure and diabetes. My long-term goal is to understand the cellular mechanisms underlying neuronal excitability, synaptic connectivity, and plasticity of central neuronal circuits involved in autonomic and neuroendocrine control. Furthermore, we aim to elucidate whether and how structural and functional remodeling within these key neuronal networks contribute as pathophysiological mechanisms in hypertension, heart failure and diabetes

Major focus interest in our laboratory include:

• Cellular mechanisms underlying synaptic connectivity, modulation, and neuroplasticity of neuronal circuits involved in autonomic and neuroendocrine control.

• Role of intrinsic ionic channels and synaptic mechanisms modulating the firing behavior of hypothalamic peptidergic systems.

• Neuromodulation of ionic channels by functionally-related transmitters/hormones.

• Neuroplasticity during different physiological and pathological states, including reproductive states, stress and hypertension.

We are currently studying in an integrative and systematic fashion the role that intrinsic (ion channels, neuronal structure), synaptic (balance between synaptic excitatory and inhibitory inputs) and paracrine mechanisms play in controlling excitability in central neuroendocrine and autonomic neuronal populations, and how plasticity in these mechanisms contribute to adaptive or pathological conditions. Our work focuses on cells (neurons, astroctyes and microvascular) located in two major hypothalamic centers: The supraoptic (SON) and paraventricular (PVN) nuclei.

• Role of K+ and Ca2+ ion channels in controlling neuronal excitability of autonomic and neuroendocrine hypothalamic neurons in normotensive and hypertensive conditions.

• Mechanisms by which astrocytes modulate excitatory and inhibitory synaptic function in hypothalamic neurondocrine and autonomic neurons.

• Neuronal-glial-vascular signaling in physiological and pathological conditions.

• Hypothalamic structural and functional plasticity: a pathophysiological mechanism underlying altered neurohumoral control in disease conditions.

• Role of oxidative stress in altered synaptic function in diabetic rats.

• Central mechanisms by which exercise activity improves cardiovascular function in physiological and pathological conditions. 

• Role of nitric oxide and other gaseous molecules in fine-tuning synaptic function in autonomic and neuroendocrine neurons.

• Cellular mechanisms underlying somatodendritic peptidergic release in the hypothalamus: role in autonomic and neuroendocrine integration.

Methods

• Patch clamp electrophysiological recordings (brain slices, dissociated neurons)
• Live calcium imaging
• Immunohistochemistry (light confocal and electron microscopy)
• Neuronal tract tracing
• 3D neuronal reconstruction
• Real time RT-PCR
• Neuronal-glial-vasculature morphometry