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
• 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
|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.