Publications by authors named "Shovan Naskar"

7 Publications

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Cell-type-specific recruitment of GABAergic interneurons in the primary somatosensory cortex by long-range inputs.

Cell Rep 2021 Feb;34(8):108774

Unit on Functional Neural Circuits, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Extensive hierarchical yet highly reciprocal interactions among cortical areas are fundamental for information processing. However, connectivity rules governing the specificity of such corticocortical connections, and top-down feedback projections in particular, are poorly understood. We analyze synaptic strength from functionally relevant brain areas to diverse neuronal types in the primary somatosensory cortex (S1). Long-range projections from different areas preferentially engage specific sets of GABAergic neurons in S1. Projections from other somatosensory cortices strongly recruit parvalbumin (PV)-positive GABAergic neurons and lead to PV neuron-mediated feedforward inhibition of pyramidal neurons in S1. In contrast, inputs from whisker-related primary motor cortex are biased to vasoactive intestinal peptide (VIP)-positive GABAergic neurons and potentially result in VIP neuron-mediated disinhibition. Regardless of the input areas, somatostatin-positive neurons receive relatively weak long-range inputs. Computational analyses suggest that a characteristic combination of synaptic inputs to different GABAergic IN types in S1 represents a specific long-range input area.
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http://dx.doi.org/10.1016/j.celrep.2021.108774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995594PMC
February 2021

The development of synaptic transmission is time-locked to early social behaviors in rats.

Nat Commun 2019 03 13;10(1):1195. Epub 2019 Mar 13.

Local Micro-environment and Brain Development Laboratory, Istituto Italiano di Tecnologia, Genova, Italy.

The development of functional synapses is a sequential process preserved across many brain areas. Here, we show that glutamatergic postsynaptic currents anticipated GABAergic currents in Layer II/III of the rat neocortex, in contrast to the pattern described for other brain areas. The frequencies of both glutamatergic and GABAergic currents increased abruptly at the beginning of the second postnatal week, supported by a serotonin upsurge. Integrative behaviors arose on postnatal day (P)9, while most motor and sensory behaviors, which are fundamental for pup survival, were already in place at approximately P7. A reduction in serotonin reuptake accelerated the development of functional synapses and integrative huddling behavior, while sparing motor and sensory function development. A decrease in synaptic transmission in Layer II/III induced by a chemogenetic approach only inhibited huddling. Thus, precise developmental sequences mediate early, socially directed behaviors for which neurotransmission and its modulation in supragranular cortical layers play key roles.
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http://dx.doi.org/10.1038/s41467-019-09156-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416358PMC
March 2019

Developmental refinement of synaptic transmission on micropatterned single layer graphene.

Acta Biomater 2018 Jan 6;65:363-375. Epub 2017 Nov 6.

Department of Nanophysics, Istituto Italiano di Tecnologia, Genova, Italy. Electronic address:

Interfacing neurons with graphene, a single atomic layer of sp hybridized C-atoms, is a key paradigm in understanding how to exploit the unique properties of such a two-dimensional system for neural prosthetics and biosensors development. In order to fabricate graphene-based circuitry, a reliable large area patterning method is a requirement. Following a previously developed protocol, we monitored the in vitro neuronal development of geometrically ordered neural network growing onto patterned Single Layer Graphene (SLG) coated with poly-D-lysine. The microscale patterns were fabricated via laser micromachining and consisted of SLG stripes separated by micrometric ablated stripes. A comprehensive analysis of the biointerface was carried out combining the surface characterization of SLG transferred on the glass substrates and Immunohistochemical (IHC) staining of the developing neural network. Neuronal and glial cells proliferation, as well as cell viability, were compared on glass, SLG and SLG-patterned surfaces. Further, we present a comparative developmental study on the efficacy of synaptic transmission on control glass, on transferred SLG, and on the micropatterned SLG substrates by recording miniature post synaptic currents (mPSCs). The mPSC frequencies and amplitudes obtained on SLG-stripes, SLG only and on glass were compared. Our results indicate a very similar developmental trend in the three groups, indicating that both SLG and patterned SLG preserve synaptic efficacy and can be potentially exploited for the fabrication of large area devices for neuron sensing or stimulation.

Statement Of Significance: This paper compares the morphological and functional development of neural networks forming on glass, on Single Layer Graphene (SLG) and on microsized patterned SLG substrates after neuron spontaneous migration. Neurons developing on SLG are viable after two weeks in vitro, and, on SLG, glial cell proliferation is enhanced. The functionality of the neural networks is demonstrated by measuring the development of neuron synapses in the first and second week in vitro. Preserving the neuron synaptic efficacy, both homogeneous and patterned interfaces based on graphene can be potentially exploited for the fabrication of large area devices for neuron sensing or stimulation, as well as for next generation of bio-electronic systems, to be used as brain-interfaces.
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http://dx.doi.org/10.1016/j.actbio.2017.11.005DOI Listing
January 2018

Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome.

Nat Med 2015 Apr 16;21(4):318-26. Epub 2015 Mar 16.

Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability, and altered GABAergic transmission through Cl(-)-permeable GABAA receptors (GABAARs) contributes considerably to learning and memory deficits in DS mouse models. However, the efficacy of GABAergic transmission has never been directly assessed in DS. Here GABAAR signaling was found to be excitatory rather than inhibitory, and the reversal potential for GABAAR-driven Cl(-) currents (ECl) was shifted toward more positive potentials in the hippocampi of adult DS mice. Accordingly, hippocampal expression of the cation Cl(-) cotransporter NKCC1 was increased in both trisomic mice and individuals with DS. Notably, NKCC1 inhibition by the FDA-approved drug bumetanide restored ECl, synaptic plasticity and hippocampus-dependent memory in adult DS mice. Our findings demonstrate that GABA is excitatory in adult DS mice and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS.
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http://dx.doi.org/10.1038/nm.3827DOI Listing
April 2015

Early depolarizing GABA controls critical-period plasticity in the rat visual cortex.

Nat Neurosci 2015 Jan 8;18(1):87-96. Epub 2014 Dec 8.

Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.

Hyperpolarizing and inhibitory GABA regulates critical periods for plasticity in sensory cortices. Here we examine the role of early, depolarizing GABA in the control of plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical-period plasticity in visual cortical circuits without affecting the overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, downregulation of brain-derived neurotrophic factor (BDNF) expression and reduced density of extracellular matrix perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and a pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.
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http://dx.doi.org/10.1038/nn.3890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338533PMC
January 2015

Mechanism(s) of deep brain stimulation and insights into cognitive outcomes in Parkinson's disease.

Brain Res Rev 2010 Oct 10;65(1):1-13. Epub 2010 May 10.

Department of Physiology, All India Institute of Medical Sciences, New Delhi-29, India.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. Deep brain stimulation (DBS) at high frequency is now considered the most effective neurosurgical therapy for movement disorders, especially PD. An electrode is chronically implanted in a particular area of the brain and, when continuously stimulated, it significantly alleviates motor symptoms. In Parkinson's disease, the common target nuclei of high frequency stimulation (HFS) are the basal ganglia nuclei, such as the internal segment of the pallidum and the subthalamic nucleus (STN), with a preference for the STN in recent years. Two fundamental mechanisms have been proposed to underlie the beneficial effects of HFS: either silencing or excitation of STN neurons. This article highlights the recent views concerned with the mechanisms of DBS. Although the efficacy of DBS for the motor symptoms of advanced PD is well established, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The cognitive aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. This article also reviews the published literature on the cognitive aspects of DBS for PD.
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http://dx.doi.org/10.1016/j.brainresrev.2010.04.010DOI Listing
October 2010

Effect of acute deep brain stimulation of the subthalamic nucleus on auditory event-related potentials in Parkinson's disease.

Parkinsonism Relat Disord 2010 May 8;16(4):256-60. Epub 2010 Feb 8.

Department of Physiology, Cognitive Neurophysiology Laboratory, All India Institute of Medical Sciences, New Delhi 29, India.

Objective: The analysis of long-latency event-related potentials (ERPs) is an important approach in the evaluation of certain cognitive functions, particularly selective attention, and in following their subsequent changes. Auditory P300 has previously been reported to be abnormal in patients with Parkinson's disease (PD). The aim of this study was to investigate whether acute deep brain stimulation (DBS) of the subthalamic nucleus (STN) itself can cause changes in the configuration of ERPs.

Method: Using a standard auditory oddball paradigm, we elicited ERPs in 10 patients with PD (in both DBS-ON and DBS-OFF conditions). The patients acted as their own controls. The N100, P200, N200 and P300 latencies, amplitudes and areas were compared between DBS-ON and DBS-OFF states. The motor reaction times were also recorded and compared between the two states.

Results: Comparison of the DBS-ON and DBS-OFF states revealed that neither amplitudes nor areas of the ERP components changed significantly; however, significant changes were observed in the latency of N100 potential when the target stimulus was applied, although there was no significant change in the latency of the P300 potential. No significant changes were noted in the latencies of the other observed ERP components. There was a marked improvement in the reaction time after the DBS electrode was turned ON.

Conclusion: Our data indicate that DBS might have varied impacts on electrophysiological parameters during the auditory oddball paradigm. Moreover, it may also worsen the orientation response as reflected by the increase in the N100 latency after the DBS electrode is turned ON.
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http://dx.doi.org/10.1016/j.parkreldis.2009.12.006DOI Listing
May 2010