The connectome of medullary sympathetic premotor neurons
thesisposted on 2022-03-28, 15:03 authored by Bowen Richard Dempsey
The basal and evoked activity of sympathetic nerves, and therefore the physiological consequences of sympathetic nerve activity (e.g. cardiovascular homeostasis), are directly dependent on synaptic drive arising from groups of sympathetic premotor neurons in the medulla and hypothalamus. The central theme of this thesis is the employment of genetic tools, primarily viral based tracing strategies, to map the locations of neurons distributed throughout out the brain that provide synaptic drive to sympathetic premotor neurons in the ventral medulla. Genetic tools grant researchers the ability to selectively manipulate neuronal populations based on either anatomical criteria or the constitutive expression of specific promoters. In Chapter 2 of this thesis we developed a novel technique that permits the genetic manipulation of single neurons in the rat, based on functional (electrophysiological) criteria. The work described in this chapter is foundational for future experiments that intend to map functionally relevant circuits in combination with tran-synaptic viral tracing strategies. Sympathetic premotor neurons within the rostral ventrolateral medulla (RVLM) are essential for the generation of vasomotor tone. However, key questions regarding the architecture of the circuits that control their activity remain. In Chapter 3 we address this topic by employing a trans-synaptic viral tracing strategy to identify neurons monosynaptically connected to bulbospinal RVLM neurons. The anatomical data acquired using this approach has allowed us to generate a brainwide map of the neurons that provide monosynaptic input to bulbospinal RVLM neurons, and therefore determine major sources of synaptic drive likely to underlie the generation of SNA. We describe an arrangement for afferent input to RVLM bulbospinal neurons that emphasises input from hitherto unappreciated local medullary sources, but is overall qualitatively similar to currently held circuit schemes. In Chapter 4 we examine the anatomical substrates that underlie the recruitment of autonomic and motor responses to alerting stimuli. Using an anterograde viral tracing strategy we identify a previously undescribed direct efferent projection from the superior and inferior colliculi to the ventral brainstem. We describe termination of axons originating from the colliculi to regions of the brainstem previously associated with sympathetic, respiratory, and motor functions, and observe putative synaptic contacts in close apposition to bulbospinal neurons in the rostral ventromedial medulla and medullary raphe nuclei. These observations characterize a potential pathway via which sympathetic, respiratory and motor outflows are coordinated by higher order sensory systems. The application of genetic approaches in the context of autonomic systems provides an unprecedented opportunity to examine the structure of discrete neural circuits that drive a defined, measurable output. The experiments conducted in this thesis provide a greater understanding of the neuroanatomy that underlies the central control of physiological behaviours, specifically the basal control of blood pressure and the coordination of sympathetic outputs as component of motor responses to the environment.