Effects of neural activity modulation and cranial window implantation on murine brain temperature
Open Access
- Author:
- Recalde Phillips, Sarea
- Millennium Scholars Program:
- Biomedical Engineering (BME)
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisor:
- Patrick James Drew, Thesis Supervisor
- Keywords:
- CBF
brain temperature
neural activity
cranial window
DREADDs
neural modulation
thermocouple
CNO
DMSO
muscimol
L-NAME
aCSF - Abstract:
- The brain is a temperature-sensitive organ that needs to be within a narrow temperature range to function properly. The regulation of proper regulation of brain temperature is essential, but the mechanisms controlling brain temperature are not well understood. Cerebral blood flow (CBF) has been hypothesized to maintain local temperature by carrying heat away from active brain regions. Increases in neural activity generates heat, and these increases are coupled with CBF fluxes. Furthermore, the structure of the head allows for brain temperature to not be instantly and drastically affected by the external environment. In this study, we aimed to investigate the effect of independently manipulating CBF and neural activity on local brain temperature. We also aimed to investigate the effect surface brain temperature when part of a murine skull was thinned to create a cranial window. Brain temperature in awake mice was measured with a K-type thermocouple implanted in the cortex. Prior to CBF and neural modulation, the first study consisted of verifying that dimethyl sulfoxide (DMSO) and clozapine-n-oxide (CNO) do not affect brain temperature when administered intravenously in murine models. In the second study we studied the effect of blood flow and neural activity on temperature by utilizing the GABAA agonist muscimol to decrease both via local infusions. We explored the contribution of blood flow on temperature by decreasing blood flow without changing neural activity with the nitric oxide synthase inhibitor L-NAME. We compared any temperature changes evoked by drug infusions to artificial cerebrospinal fluid (aCSF), the vehicle control. The first study demonstrated that CNO and DMSO do not have a substantial effect on brain temperature, thereby verifying their use in designer receptors exclusively activated by designer drugs (DREADDs)-containing mice. We found that brain temperature insignificantly decreased in response to independent modulation of cerebral blood flow, neural activity, and a combination of the two. These brain temperature changes were, however, less than a degree. Despite the second and third studies, these changes did not provide a significant influence on brain temperature. The fourth study demonstrated the most dramatic change in temperature, with brain temperature decreasing as low as 2◦C once water was added to the window.