Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Abstract

Prenatal cannabis exposure is as common as prenatal alcohol exposure, and yet it is understudied. With the recent legalization of cannabis, it is doubly important to elucidate these effects. The hippocampus is rich in cannabinoid type 1 receptors, which are targeted by the psychoactive component of cannabis. The hippocampus is central to learning and memory and is known to be affected acutely by this drug. In this dissertation, I examine how prenatal THC exposure affects different populations of hippocampal interneurons, how morphological characteristics of microglia are altered, and hippocampal synaptic plasticity is affected, and how inhibitory and excitatory markers My findings show not only that there are alterations in all these areas, but that there are regional and sex differences in many of these changes. These results suggest that there is increased GABAA recruitment via increased gephyrin cluster sizes. In absence of other receptor changes this shows that the balance of inhibition and excitation is shifted towards inhibition. Dendritic spines decreases are consistent with human clinical findings with similar psychiatric outcomes. As interneuron densities are static compared with other outcome measures, early perturbations in the endocannabinoid system likely drive the observed interneuron alterations, which then drive spine, receptor, and plasticity alterations. This work shows that there are consequences of prenatal cannabis exposure into adulthood.

Repeated mild traumatic brain injury causes sex-specific increases in cell proliferation and inflammation in juvenile rats

“…All animals were administered either an ACHI, or exposed to the sham procedure, eight times over a 16-h period. All subjects were assessed for a series of four sensorimotor and reflex tasks (startle response, limb extension, beam walk and rotating beam walk), administered immediately following each ACHI/sham procedure as a neurological assessment procedure (NAP) [ 68 , 69 ]. There were no sex differences or differences between groups at baseline (Fig.…”

“…after blinding for subject identity was removed. Experiments were conducted using a modified CCI device and the modifications are described elsewhere [ 22 , 69 ]. All other reagents are available commercially, and detailed staining protocols are available upon request.…”

“…The goal of the current study was to standardize post-injury days given that previous cell proliferation studies result in transient changes [ 66 , 67 ]. The ACHI procedure was performed as previously described [ 68 , 69 ]. In brief, animals were immobilized using a clear plastic restraint cone.…”