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Karkare, S.

Publications and source records attributed to Karkare, S..

4 recordsLinked to original sources

Organization of brainwide inputs to discrete lateral septum projection populations

The lateral septum (LS) is anatomically positioned to play a critical role in directing information from the hippocampus and cortex to downstream subcortical structures, such as the hypothalamus. In fact, early anatomical tracing studies investigated the organization of hippocampal inputs to the LS and its hypothalamic outputs to begin to understand how its structure might relate to its function. These studies also characterized the cellular anatomy of the LS and the organization of different molecular markers within it. However, relatively little is known about the organization of other, non-hypothalamic projection populations within the LS and what types of input these different projection populations receive. Here, we used retrograde tracing to determine the organization of LS projections to six different brain regions that mediate various social behaviors. We found that these projection populations occupy discrete anatomical compartments within the LS. We then used a monosynaptic rabies tracing strategy to map brainwide inputs to these six discrete LS projection populations and examine how different brain regions innervate them. We identified unique region-dependent patterns of inputs to individual LS projection populations. In particular, we observed differences in cortical, hippocampal and thalamic innervation of the six different LS projection populations, while the hypothalamic inputs were largely similar across projection populations. Thus, this study provides insight into the anatomical connectivity that may underlie the functional heterogeneity of the LS.

neuroscience↗

A ventral hippocampal-lateral septum pathway regulates social novelty preference.

The ability to distinguish strangers from familiar individuals is crucial for the survival of most mammalian species. In humans, an inability to recognize kin and familiar individuals and engage in appropriate behaviors is associated with several types of dementia, including Alzheimers disease. Mice preferentially spend more time investigating a novel individual relative to a familiar individual. Yet, how social novelty related information drives increased investigation of the novel animal remains poorly understood. Recent evidence has implicated the ventral hippocampus (vHPC) as a key node in encoding information about conspecific identity. Of particular interest are vHPC projections to the lateral septum (LS), a region that has been implicated in driving a wide range of motivated social behaviors. In this study using chemogenetics, optogenetics and monosynaptic rabies tracing, we identified a novel vHPC-LS-ventral tegmental area (VTA) pathway that is necessary for mice to preferentially investigate novel conspecifics. Using monosynaptic rabies tracing, we established that LS neurons make direct monosynaptic connections onto dopaminergic neurons in the VTA. Thus, we have identified a potential pathway via which conspecific identity could be transformed to drive motivated social behaviors.

neuroscience↗

Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex.

The reinforcing nature of social interactions is necessary for the maintenance of appropriate social behavior. However, the neural substrates underlying social reward processing and how they might differ based on the sex and internal state of the animal remains unknown. It is also unclear whether these neural substrates are shared with those involved in nonsocial rewarding processing. We developed a fully automated, novel two choice (social-sucrose) operant assay in which mice choose between social and nonsocial rewards to directly compare the reward-related behaviors associated with two competing stimuli. We performed cellular resolution calcium imaging of medial prefrontal cortex (mPFC) neurons in male and female mice across varying states of water restriction and social isolation. We found that mPFC neurons maintain largely non-overlapping, flexible representations of social and nonsocial reward that vary with internal state in a sex-dependent manner. Additionally, optogenetic manipulation of mPFC activity during the reward period of the assay disrupted reward-seeking behavior across male and female mice. Thus, using a novel operant assay, we have identified sex-dependent, non-overlapping neural representations of social and nonsocial reward in the mPFC that vary with internal state and that are essential for appropriate reward-seeking behavior.

neuroscience↗

The application of text mining algorithms in summarizing trends in anti-epileptic drug research

1.Content summarization is an important area of research in traditional data mining. The volume of studies published on anti-epileptic drugs (AED) has increased exponentially over the last two decades, making it an important area for the application of text mining based summarization algorithms. In the current study, we use text analytics algorithms to mine and summarize 10,000 PubMed abstracts related to anti-epileptic drugs published within the last 10 years. A Text Frequency - Inverse Document Frequency based filtering was applied to identify drugs with highest frequency of mentions within these abstracts. The US Food and Drug database was scrapped and linked to the results to quantify the most frequently mentioned modes of action and elucidate the pharmaceutical entities marketing these drugs. A sentiment analysis model was created to score the abstracts for sentiment positivity or negativity. Finally, a modified Latent Dirichlet Allocation topic model was generated to extract key topics associated with the most frequently mentioned AEDs. Results of this study provide accurate and data intensive insights on the progress of anti-epileptic drug research.

systems biology↗