Research Interests

Virginia setup

Maryland setup

The specific pattern of electrical activity observed in a neuron is dictated by the complement of ion channels expressed by the cell and by the synaptic inputs that it receives. Chemicals in the brain (that is, neurotransmitters and drugs) change those patterns of activity, often by modulating the behavior of ion channels postynaptically or by presynaptic modulation of neurotransmitter release. My research focuses on investigating catecholaminergic modulation of neuronal excitability through direct actions on membrane properties or by modulating excitatory and inhibitory synaptic release. I have been interested in studying the function of the noradrenergic system at the cellular level in two brain structures: the rostral ventrolateral medulla and the olfactory bulb.

The rostral ventrolateral medulla (RVL) plays a pivotal role in the control of sympathetic tone and arterial pressure and in the maintenance of normal cardiorespiratory activity.
Virtually all neurophysiological studies devoted to this structure have focused on a small number of efferent neurons which project to the spinal cord. These few hundred neurons consist of C1 catecholaminergic neurons and other neurons (non-C1). These neurons project to the intermediolateral cell column (IML) and maintain resting levels of arterial pressure by exciting sympathetic preganglionic neurons.

Moreover, neurons in the C1 area initiate the cardiovascular response to ischemia, and mediate rapid sympathoexcitatory pressor response to acute hypoxia. On the other hand, there is now good evidence that the key mechanisms for breathing rhythm generation resides within the RVL where several neuron types likely to support the rhythm generating process have been identified.
Receptors in the RVL are responsive to a broad spectrum of cardioactive agents and the RVL is a major site of action of the imidazole, clonidine - a clinically effective antihypertensive drug. Nonetheless, still there is a lot of doubt concerning the identity of the neurotransmitter in the RVL generating sympathetic tone. Also, it is not yet resolved whether it is, in fact, the C1 neurons of RVL which contribute to exaggerated sympathetic tone and in turn, the circulatory changes involved in the initiation, expression or maintenance of neurogenic hypertension.
In sum, RVL reticulospinal sympathoexcitatory neurons are multifaceted in their actions. The objectives of the current investigations of the functions and roles of RVL neurons is to provide significant information that could explain why and when the central nervous system fails to maintain the normal functions and how such abnormality can be corrected and prevented.

I have investigated pre- and postsynaptic actions of opioid and adrenergic receptor agonists (including centrally-acting antihypertensive drugs) on RVL bulbospinal neurons in brainstem slices. My major findings were the following:
• The majority of C1 and non-C1 RVL bulbospinal neurons are inhibited by met-enkephalin via activation of µ-opioid receptors.
• The inhibition of RVL neurons by opioids occurs:
- Postsynaptically: Opening of inwardly rectifying potassium channels.
- Presynaptically: Decrease of glutamatergic transmission.
• These mechanisms could explain the hypotensive and sympathoinhibitory actions of opioids transmitters in the RVL in particular during hypotensive hemorrhage.
• NE inhibits bulbospinal RVL neurons by activating alpha2-adrenoceptors (alpha2-ARs) located postsynaptically and presynaptically on glutamatergic terminals.
• Contrary to our expectations, alpha2-ARs were also found on GABAergic inputs to these cells.
• Unlike the postsynaptic effects, the decrease of synaptic transmission by NE was not sensitive to barium, indicating that different mechanisms of action are involved in the pre- and postsynaptic effects of NE.
• Finally, all effects of NE were mimicked by the prototypical imidazoline ligand moxonidine which was found to behave like an alpha2-AR agonist.

Picture of an RVL neuron recorded using the whole-cell patch configuration in a brainstem slice of a neonatal rat.

The main olfactory bulb (MOB) is a highly organized, well characterized, relatively simple cortical network that functions to process olfactory information. It receives a significant modulatory noradrenergic input from the locus coeruleus which densely innervates this network with a higher degree of laminar specificity than in any other forebrain target. Previous in vivo and in vitro work showed that norepinephrine (NE) increases the sensitivity of mitral cells to weak olfactory inputs. The goal of my current research is to investigate the cellular basis for this action of NE in olfactory bulb slices and to identify the type of adrenergic receptor involved in regulating the excitability of mitral cells, the main output of the olfactorybulb.

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