Bains, JaideepRasiah, Neilen Paul2019-09-132019-09-132019-08-30Rashiah, N. P. (2019). Assessing Functional Roles for Synaptic Scaling and Local Processing in CRHPVN Neurons (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/110917The brain, comprised of billions of neurons in highly-interconnected networks, receives information about the environment and the organism’s internal state, and makes ongoing adjustments that allow for optimum function and information storage. These adjustments, if inappropriately managed, can also destabilize neural networks, resulting in pathology. This thesis is primarily focused on understanding mechanisms that maintain stability, while adaptive adjustments are integrated in a key stress-processing neural population, the corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN). Activation of these neurons during stress drives the production of glucocorticoids (CORT). The production of CORT is typically self-limiting, but under some conditions, CORT release continues unabated. This offers an opportunity to study underlying synaptic and cellular adjustments that contribute to stability in these circuits. I used chemogenetics to assess how CRHPVN neurons respond to decreased excitability. There was an increase in the strength of glutamatergic synapses that was consistent with multiplicative scaling, which has previously been described to maintain stability. Next, I asked whether pathophysiological manipulations would force similar adjustments to this system. I examined how persistent CORT feedback, a feature of chronic stress, influences CRHPVN neurons. Following 7 days CORT, CRHPVN neurons showed a decrease in intrinsic excitability, which coincided with multiplicative scaling at glutamate synapses. In the next chapter, I assessed population activity of CRHPVN neurons in live mice. CORT had no effect on the activity of these neurons. However, CRHPVN-neuron activity in baseline, and during mild stress, was diminished when scaling was prevented during CORT. This indicates that scaling maintains stability in these conditions. In the final data chapter, I optimized the use of miniature head-fixed microscopes to obtain the first recordings from identified CRHPVN neurons. These recordings reveal that CRHPVN neurons show disparate responses to stress. These studies provide novel information regarding the activity of CRHPVN neurons in freely behaving mice. They indicate this population is more diverse than previously described, and that individual neurons (or subpopulations) may discretely encode stressor-specific information. Furthermore, they provide the first evidence for a homeostatic scaling-like mechanism that maintains stability in the face of an internal challenge to homeostasis.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Synaptic scalingin vivo imagingHPA axisGlucocorticoidsChemogeneticsCorticotropin-releasing hormone neuronsparaventricular nucleus of the hypothalamusNeurosciencedoctoral thesis10.11575/PRISM/36989