Neurotechnologies | Icahn School of Medicine

CENTER FOR NEUROTECHNOLOGY AND BEHAVIOR

We stand at a pivotal moment in neuroscience research, where technological innovation has created unprecedented opportunities to understand the brain. Through the convergence of engineering, physics, chemistry, and biology, today's neurotechnologies allow us to observe, manipulate, and decode neural activity across multiple scales—from individual molecules to entire brain regions.

At the Icahn School of Medicine at Mount Sinai, our researchers develop and implement innovative neurotechnologies that enable us to probe fundamental questions about brain function in both health and disease. These tools allow for real-time visualization of neural activity in freely behaving subjects, targeted manipulation of specific cell types, and molecular analysis. By applying these advanced technologies to study neural circuits underlying complex behaviors and neuropsychiatric disorders, we aim to translate discoveries into novel therapeutic strategies.

Research Areas

Our researchers at the Center for Neurotechnology and Behavior are leveraging advanced imaging technologies to visualize and understand neural activity with unprecedented precision. Calcium imaging techniques are widely employed to monitor neuronal firing patterns by detecting calcium ion transients, offering insights into neural ensemble dynamics during memory formation, retrieval, and social behaviors. Miniature microscopes, particularly the open-source Miniscope technology, enable in vivo calcium imaging in freely behaving animals, representing a significant advancement over traditional methods that required restrained subjects. Optofluidic devices permit the imaging and drug delivery in real-time in vivo. Our researchers are on the forefront of merging cutting-edge technology, such as using Miniscopes, to monitor both neural activity and the release of specific neurotransmitters simultaneously.

Neuroimaging studies of the human brain examine relationships between genetic factors and neurobiological systems underlying conditions like addiction, while super-resolution imaging techniques provide detailed visualization of synaptic structures and cellular mechanisms. Single-cell omics approaches map chromatin states and gene expression patterns across diverse neuronal populations, linking cellular function to genetic profiles. These imaging technologies collectively advance our understanding of neural circuits in both healthy and diseased states, potentially leading to new therapeutic targets for neurological and psychiatric disorders.

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Center investigators are using sophisticated electrophysiological techniques to record and analyze electrical activity in neural circuits. These methods range from traditional patch-clamp recordings to in vivo electrophysiology with high-density silicon probes, providing critical insights into neuronal communication, synaptic transmission, and network dynamics. Our scientists apply these techniques to explore how genetic mutations, environmental stressors, or pharmacological interventions affect neuronal signaling, particularly in the context of neuropsychiatric disorders and addiction.

Whole-cell patch-clamp recordings of neurons from specific brain regions help researchers understand circuit-level changes in conditions like Parkinson's disease, revealing abnormalities in local circuit control and synaptic plasticity. In vivo single-unit recordings in awake, behaving animals further elucidate neural mechanisms underlying complex behaviors. The integration of electrophysiology with other methodologies, such as PATCH-seq (combining patch-clamp with single-cell RNA sequencing), links functional properties of neurons to their gene expression profiles. These approaches collectively contribute to our understanding of normal brain function and offer potential therapeutic targets for neurological and psychiatric disorders by identifying specific cellular and circuit dysfunctions.

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The Center for Neurotechnology and Behavior possesses a team of scientists employing cutting-edge genetic and molecular tools to investigate the underlying mechanisms of neurological and psychiatric disorders. CRISPR/Cas9 genome editing allows for precise genetic modifications to study specific gene functions. RNA sequencing and single-cell technologies provide comprehensive analyses of gene expression profiles influenced by genetic and environmental factors, now being applied spatially. Viral-mediated gene transfer techniques enable targeted manipulation of gene expression within specific brain regions, facilitating the study of their roles in conditions like addiction and depression.

Locus-specific epigenome editing gives us precise modifications of the epigenome at specific genomic loci, allowing researchers to investigate causal links between epigenetic changes and behavioral outcomes. Our team develops novel chemical methodologies and engineered proteins to probe chromatin-based mechanisms in neurons, as well as investigate structural and functional aspects of ion channels crucial for neuronal signaling. These molecular approaches enhance our understanding of the genetic and molecular underpinnings of brain function and dysfunction, paving the way for more targeted therapeutic interventions for neurological and psychiatric disorders.

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Our researchers at the Center for Neurotechnology and Behavior are utilizing advanced circuit manipulation technologies to causally link neural circuit activity with behavior and disease states. Optogenetic approaches employ light to precisely control specific types of neurons, allowing our scientists to investigate causal relationships in memory circuits, perception, cognition, and social behavior. Chemogenetic methods involve engineered receptors and designer drugs to selectively activate or inhibit specific neuronal populations over extended periods, providing insights into how neural circuits regulate complex behaviors.

In non-human primates, chemogenetic approaches help us understand brain function in models more closely resembling human neuroanatomy, accelerating translational potential. Closed-loop systems with real-time processing algorithms enable activation or inhibition of neurons with millisecond precision, exploring how precise timing of neural activity controls cognition and behavior. These technologies are being applied to understand normal brain function and develop targeted interventions for conditions ranging from addiction and depression to diabetes and autism spectrum disorders. For instance, chemogenetic activation of vagal nerves within the pancreas has been shown to lower blood glucose without causing hypoglycemia, suggesting a potential therapeutic approach for diabetes.

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Mount Sinai physician-scientists are conducting extensive behavioral and translational research to bridge basic neuroscience findings with clinical applications. Behavioral analysis in rodent models helps evaluate the impact of molecular, cellular, and circuit-level manipulations on outcomes relevant to neuropsychiatric disorders, including social behavior deficits, depression, anxiety, and addiction. These approaches range from paradigms like chronic social defeat stress to assess depression-like behaviors to specific assays for social cognition and stress responses. Clinical trials complement preclinical research, evaluating the therapeutic potential of innovative strategies for treating conditions like drug addiction.

Our teams are modeling psychiatric disorders using both animal models and human-derived cells, such as induced pluripotent stem cell-derived neurons, to understand disease mechanisms and identify potential therapeutic targets. For example, our research teams are investigating how autism-associated mutations like those in the Shank3 gene affect brain circuits involved in social behavior and motivation. Neurotechnology development focuses on creating innovative tools like optical biosensors for detecting neurotransmitter release and open-source software for behavioral analysis, accelerating research capability across the field. This translational approach is essential for developing effective interventions for neurological and psychiatric disorders by ensuring findings from basic research can be applied to clinical settings.

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