The aim of this research is to investigate the role of brain-produced cannabinoids in how the world is perceived at the level of the first stage of sensory processing in the brain. Sensory system processing is critical for an animal's ability to function within an environment. Humans and higher predator species are primarily visually oriented but most lower animal species utilize olfaction, the sense of smell, as a primary sensory modality. The ability of the olfactory system to detect a huge array of chemicals across wide concentration ranges is a formidable brain processing task. Processing of odor information in the first brain relay station, the main olfactory bulb, is a major contributor to this striking dynamic range. The experiments will increase the understanding of olfactory processing with potential impact on other sensory systems with similar circuit building mechanisms. Understanding the action of cannabinoids on sensory processing will shed light on how cannabinoids lead to altered sensory perception. Rather than purely higher order hallucinogenic action, the experiments will reveal how primary sensory modulation is influenced by cannabinoids and may lead to a better understanding of drug seeking behaviors. This research will provide an educational and outreach experience of exceptional quality for students at all levels with an emphasis on minority students at Howard University. The aim is to broaden the participation of students with minority background to expand the population of minority students as the science workforce of the future.
Marijuana (cannabis) is the most commonly abused illicit drug in the USA. Its bioactive ingredient, THC, activates cannabinoid receptors in the brain in the same manner as brain-produced endogenous cannabinoids (endocannabinoids). The endocannabinoid system is an important intrinsic neuromodulatory system during normal brain function and impacts sensory processing. The experiments take advantage of the highly laminar organization of the main olfactory bulb and a growing body of knowledge on how this system processes sensory information. This research will investigate the role of endocannabinoids in the olfactory system using whole-cell patch-clamp recordings, signal imaging and various mouse strains. Specifically, the research will explore how endocannabinoids regulate the activity of output neuron sensitivity and dynamic range in the main olfactory bulb. This will be followed by studying if environmental conditions such as a change in olfactory input engage endogenously produced cannabinoids. The researchers will exploit olfactory deprivation to identify the cellular, membrane, pharmacologic and network properties of endocannabinoid-modulated neural processing in the main olfactory bulb.
