Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. In addition, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches--Daun02 inactivation, FACS sorting of activated neurons and Fos-GFP transgenic rats--that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools--Fos-tTA transgenic mice and inactivation of CREB-overexpressing neurons--that have been used to study the role of neuronal ensembles in conditioned fear.
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http://dx.doi.org/10.1038/nrn3597 | DOI Listing |
Neurophotonics
January 2025
University of Pittsburgh, Department of Psychiatry, Translational Neuroscience Program, Pittsburgh, Pennsylvania, United States.
Internal states involve brain-wide changes that subserve coordinated behavioral and physiological responses for adaptation to changing environments and body states. Investigations of single neurons or small populations have yielded exciting discoveries for the field of neuroscience, but it has been increasingly clear that the encoding of internal states involves the simultaneous representation of multiple different variables in distributed neural ensembles. Thus, an understanding of the representation and regulation of internal states requires capturing large population activity and benefits from approaches that allow for parsing intermingled, genetically defined cell populations.
View Article and Find Full Text PDFNat Methods
January 2025
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Teravoxel-scale, cellular-resolution images of cleared rodent brains acquired with light-sheet fluorescence microscopy have transformed the way we study the brain. Realizing the potential of this technology requires computational pipelines that generalize across experimental protocols and map neuronal activity at the laminar and subpopulation-specific levels, beyond atlas-defined regions. Here, we present artficial intelligence-based cartography of ensembles (ACE), an end-to-end pipeline that employs three-dimensional deep learning segmentation models and advanced cluster-wise statistical algorithms, to enable unbiased mapping of local neuronal activity and connectivity.
View Article and Find Full Text PDFRecording and manipulating neuronal ensembles that underlie cognition and behavior is challenging. FLARE is a light- and calcium-gated transcriptional reporting system for labeling activated neurons on the order of minutes. However, FLARE is limited by its sensitivity to prolonged neuronal activities.
View Article and Find Full Text PDFThe idea of self-organized signal processing in the cerebral cortex has become a focus of research since Beggs and Plentz reported avalanches in local field potential recordings from organotypic cultures and acute slices of rat somatosensory cortex. How the cortex intrinsically organizes signals remains unknown. A current hypothesis was proposed by the condensed matter physicists Bak, Tang, and Wiesenfeld when they conjectured that if neuronal avalanche activity followed inverse power law distributions, then brain activity may be set around phase transitions within self-organized signals.
View Article and Find Full Text PDFBDNF plays a crucial role in shaping the structure and function of neurons. BDNF signaling in the dorsolateral striatum (DLS) is part of an endogenous pathway that protects against the development of alcohol use disorder (AUD). Dysregulation of BDNF levels in the cortex or dysfunction of BDNF/TrkB signaling in the DLS results in the escalation of alcohol drinking and compulsive alcohol use.
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