Sai Sachin Divakaruni, Ph.D.

 Sai Divakaruni


Area of Doctoral Study: Neuroscience, Medical Scientist Training Program (UMB)

Undergraduate University of Maryland, Baltimore County (UMBC)

Research Advisor: Thomas A. Blanpied

Description of Research

Modulation of neuronal synaptic strength is believed to underlie learning and memory (Bliss & Collingridge 1993), and disruption of synaptic transmission and plasticity are implicated in many neuropsychiatric diseases such as autism spectrum disorder and schizophrenia (Won et al. 2013; Zoghbi & Bear 2012). Synaptic function is energy consuming and requires large amounts of ATP (Harris et al. 2012). Because the bulk of our ATP is produced by mitochondria, the appropriate distribution of mitochondria at synapses is believed to be critical. Indeed, ATP from presynaptic mitochondria is critical for synaptic vesicle cycling (Rangaraju et al. 2014), and mitochondria are recruited to dendritic spines during synaptic potentiation (Li et al. 2004). However, mitochondrial dynamics are not limited to motility. Mitochondria also undergo fusion, to remain healthy, and fission, which is critical for neuronal development and synapse formation (Lathrop & Steketee 2013; Liu & Shio 2008). However, the role of mitochondrial fission in synaptic transmission and plasticity is little explored, particularly postsynaptically. Mitochondrial fission is a complex process controlled by interactions with the endoplasmic reticulum, actin, and cytosolic factors. A central protein in this process is the GTPase dynamin-related protein 1 (Drp1) (Smirnova et al. 2001). I study the role and regulation of Drp1 during and following induction of long-term potentiation (LTP) in cultured hippocampal neurons and, driven by preliminary data, I hypothesize that LTP requires an increase in mitochondrial fission via direct regulation of Drp1 function. Because these proteins and organelles are extremely small, the diffraction limit of light prevents adequate resolution of their structure and dynamics through traditional confocal imaging. To overcome this limitation, I use a combination of diffraction-limited confocal microscopy and the diffraction-unlimited super-resolution microscopy techniques, PALM and dSTORM.