Synaptic connections and electrophysiological properties of neurones in the intermedius nucleus of the medulla oblongata

Experiments in our laboratory have brought to our attention a collection of nerve cells (neurones) whose function is unknown. The neurones are located in a discrete region in the brainstem, the part of the brain that controls body systems critical for breathing and cardiovascular maintenance. The nucleus in which the neurones reside is known to receive information from neck muscles when they are stretched, but what this information is used for needs to be determined. Our preliminary evidence supports at least two ideas for cells in this nucleus / signalling neck muscle stretching to circuits involved in cardiorespiratory control and/or those involved in co-ordinating swallowing and breathing. To help determine if the cells participate in controlling such functions, we will investigate what other brain regions they send information to and receive information from using contemporary neuroanatomical methods. This will involve identifying cell types in the other brain regions where possible. We will also closely investigate the anatomical and electrical properties of the cells themselves since these features infleunce how the cells respond to incoming information and therefore how this information is passed on to other neurones. These studies will therefore clarify the connections and functions of an unexplored brain nucleus that we propose is involved in controlling important body functions.

Almost 100 years ago Cajal named a circumscribed nucleus in the brainstem located at the dorsolateral aspect of the hypoglossal nucleus and just ventrolateral to the dorsal vagal nucleus as the intermediate nucleus of the medulla (InM). Little has been discovered on the function or anatomy of this nucleus since that time, although it is known that the InM receives inputs from stretch receptor afferents from neck muscles. Neck stretch receptor activation has several effects, including changes in cardiorespiratory variables. However, the neuronal circuitry underlying these changes is unknown. Our preliminary evidence indicates a possible route for these effects through the InM since this nucleus contains excitatory and inhibitory neurones that project to the nucleus tractus solitarius, the major autonomic integratory area in the brainstem. Other published data could indicate that neurones in the InM are presynaptic to hypoglossal motor neurones that control tongue movements and they may be interposed between these cells and higher brain inputs. To increase understanding of the InM neurones we propose to utilise neuroanatomical methods, including immunohistochemistry, neuronal tract tracing and light and electron microscopy, to determine their organisation as well as their inputs and outputs. Since the responses of cells to synaptic inputs also rely on their intrinsic electrophysiological characteristics we also propose to investigate these with in vitro brainstem slice experiments. Experiments will be performed in rats, but also will be facilitated by use of transgenic mice engineered to produce GFP in neurones that express GAD-67 or VGluT2 and that are inhibitory and excitatory respectively. These studies will be the first comprehensive investigations into this nucleus and pathways and will therefore provide completely new information regarding its possible functions.