The purpose of this application is to support a postdoctoral training plan involving research that aims to reveal how serotonin neurotransmission controls rhythmic activity in the forebrain, specifically in the context of stres. It is widely accepted that 5HT neurons originating in the dorsal raphe nucleus (DRN) are involved in several stress-related psychiatric illnesses, such as anxiety disorders, schizophrenia, drug addiction, and especially depression. Hippocampal volume loss is a consistent observation in depressed patients, and this brain region also shows serotonin-specific changes after chronic stress. Rhythmic sinusoidal activity generated by hippocampal neurons in the theta 4-10 Hz frequency range predominates during preparatory, orienting, or exploratory movements, and is associated with cognitive functions such as learning and memory. The median raphe nucleus is known to be a powerful modulator of hippocampal theta rhythms through the septohippocampal pathway, but the role of the DRN is unknown, although there are direct connections between the caudal portion of the DRN with the septum and the hippocampus. Data from our lab suggests reciprocal control of the caudal and rostral poles of the DRN such that stimulation of one region inhibits the other, and vice versa. Thus, the main goal of this project is to determine the roles o the rostral and caudal subregions of the DRN on hippocampal theta activity basally, and in the context of stress. Serotonin is thought to be involved in the coping strategy adopted during stress, so this project will also measure behavioral activity during the forced swim test. To accomplish the goals of this project, designer receptors activated by designer drugs (DREADDs) will be used to activate or inhibit specific subregions of the DRN while simultaneously recording hippocampal activity using electroencephalography. Separate experiments will use this same approach in different behavioral contexts: in anesthetized (to measure reticular-stimulated theta rhythms), freely moving, and acutely stressed animals.
The first aim focuses on the influence of the DRN on hippocampal theta activity in anesthetized and freely moving animals, and the second aim focuses on the relationship between the DRN, hippocampal theta, and coping strategy during stress. We hypothesize that activation of the caudal and inhibition of the rostral DRN will desynchronize theta, and that this will also promote passive coping strategy during stress. The results from this project may ultimately lead to a greater understanding of the neurobiological mechanisms underlying the involvement of serotonin in many psychopathologies, particularly depression.
This goal of this research is to reveal how serotonin neurotransmission controls rhythmic activity in the forebrain, specifically in the context of stres. Serotonin is implicated in the control of stress-related affective disorders, particularly depression. Using a combination of molecular, neuroanatomical, and neurophysiological methods and focusing on relevant behavioral endpoints, the results from this project may ultimately lead to a greater understanding of the neurobiological mechanisms underlying the involvement of serotonin in several psychopathologies.
| Babb, Jessica A; Linnros, Sofia E; Commons, Kathryn G (2018) Evidence for intact 5-HT1A receptor-mediated feedback inhibition following sustained antidepressant treatment in a rat model of depression. Neuropharmacology 141:139-147 |
| Kroll-Desrosiers, Aimee R; Nephew, Benjamin C; Babb, Jessica A et al. (2017) Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year. Depress Anxiety 34:137-146 |
