The human brain is unparalleled in adaptive computational abilities in every aspect – from sensory perception to cognitive functions leading to complex behavior. Such abilities make the brain a unique biological machine. Understanding underlying principles of biological computation can pave the way for better artificial computing. Neurons, brain’s computational units, are wired together through synapses to form precise neural circuitry.Circuitry determinesneuronal activity, which underlies perception and brain functions ranging from reflexes to complex behavior. To interact with a constantly changing environment neuronal circuits are remodeled.Changes in synaptic connections (synaptic plasticity) enable adaptationto new experience and varied cognitive demands of different contexts. We present our results on mechanisms and effects of synaptic plasticity at a systemas well as cellular level. In the first part, auditory cortical response properties and circuitry is used as a model sensory system. Adaptation of circuits and hence responses can take place in long as well as rapid time scales. Developmental experience based pruning of micro-circuitryon long time scales and cognitive input based rapid plasticity in auditory cortex (ACX) circuitry and response changes are presented.We show how, on longer time scales functional micro-circuitry is shaped with onset of sound experience during development. Next, we show how response properties and micro-circuitry in ACX changesfunctionally in a rapid plasticity paradigm. In this case, we use the prefrontal cortex (PFC), a higher order brain region,involved in reward based learning, decision making, attention and reward associations as the source of modulatory inputs. With micro activation of PFC paired with specific sound stimulation we find remarkable rapid changes of tuning properties of neurons within ACX specific to the pairing sound stimulus, which changes the functional micro-organization within the ACX. Thus PFC plays a role in mediating auditory cortical plasticity in the form of changes in tuning properties of auditory cortical neurons. Collectively, these experiments provide insight into topographic organization in ACX and how such organization changes through top-down control of auditory processing. Towards the regulatory mechanism of synaptic plasticity, spatio-temporal regulation of dendritic protein synthesis has emerged as a key modulator. Neuronal activity can induce new protein synthesis at discrete locations along the dendrite that results in persistent structural, physiological, and biochemical changes in dendritic spines. Among known modulators of synaptic protein synthesis, the reversibility of microRNA (miRNA), a class of non-coding RNA, -mediated regulation of their targets makes them perfect candidates for activity-dependent translational control point of synaptic plasticity. However, molecular mechanism of non-coding RNA -mediated regulation of synaptic functions remains largely unknown. Recently, our study has elucidated a novel molecular mechanism by which miRNAs can modulate synaptic plasticity through a proteasomal control of de novo protein synthesis at synapse. We will discuss the mechanistic details of this combinatorial control of synaptic plasticity in response to neuronal activity. Apart from these studies, we will also highlight the ongoing projects of newly set up laboratoriesthat aim to investigate novel molecular mechanisms involved in development of precise neuronal connectivity and its computational functions.
Sharba Bandyopadhyay completed his B.Tech. from IIT Kharagpur in Electronics and ElectricalCommunication Engineering in 1999. After his B.Tech., he went on to do his MS (2001) and PhD(2007) in Biomedical Engineering, from Johns Hopkins University, Baltimore, USA. For his MSand PhD, he worked with Dr. Eric Young on speech coding and nonlinear auditory processing indifferent regions of the mammalian auditory pathway. Following his doctoral studies he did a post-doctoral fellowship and was subsequently Assistant Research Scientist at University ofMaryland, College Park (UMCP) till June 2012. While in UMCP he worked on auditory corticalmicro-organization and its development using 2-photon microscopy and other optical andelectrophysiological techniques. In July 2012 Sharba Bandyopadhyay started as AssociateProfessor at National Brain Research Centre (DU) at Manesar, India. Sourav Banerjee did his bachelors degree with Honours in Botany from Presidency College, Kolkata. He moved to Madurai Kamaraj University to pursue his Masters in Biotechnology. He then joined Jawaharlal Nehru Center for Advanced Scientific Research, Bangalore for PhD. He worked with Tapas Kundu on transcriptional mechanism involved in cancer manifestation. He developed his interest in Neuroscience during his PhD and moved to Yale University to pursue his career in Neuroscience. At Yale, he worked with David Wells on molecular mechanisms of synaptic plasticity. After a stint at Yale, he moved to University of California, Santa Barbara and worked with Ken Kosik on non-coding RNA-mediated gene expression control of synaptic plasticity using biochemical and optical based approach. He started his own laboratory in May 2012 at National Brain Research Center, Manesar to investigate novel epigenetic mechanisms that modulates neuronal connectivity and its function.