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The ability to flexibly use knowledge is one cardinal feature of goal-directed behaviors. We recently showed that thalamocortical and corticothalamic pathways connecting the medial prefrontal cortex and the mediodorsal thalamus (MD) contribute to adaptive decision-making (Alcaraz et al., 2018). In this study, we examined the impact of disconnecting the MD from its other main cortical target, the orbitofrontal cortex (OFC) in a task assessing outcome devaluation after initial instrumental training and after reversal of action-outcome contingencies. Crossed MD and OFC lesions did not impair instrumental performance. Using the same approach, we found however that disconnecting the OFC from its other main thalamic afferent, the submedius nucleus, produced a specific impairment in adaptive responding following action-outcome reversal. Altogether, this suggests that multiple thalamocortical circuits may act synergistically to achieve behaviorally relevant functions.
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http://dx.doi.org/10.7554/eLife.46187 | DOI Listing |
J Neurosci
September 2025
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation reflect the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice (both male and female) expressing channelrhodopsin-2 in L6CT neurons.
View Article and Find Full Text PDFBoth sensory and non-sensory brain regions receive mixed inputs from single neurons which require decomposition and integration before proceeding through a processing hierarchy. Whether mixed input signals are used in biological neural networks to derive pure single neuron representations, or distributed as new population representations from mixed single neurons, is not clear. In this study, we measured the distribution of single neuron hue and luminance tuning in the dorsolateral geniculate nucleus (dLGN) and primary visual cortex (V1) of mice, as well as the information about and structure of hue and luminance representations in populations of hundred of simultaneously sampled neurons.
View Article and Find Full Text PDFExp Physiol
September 2025
Department of Neurology, Dell Medical School at The University of Texas at Austin, Austin, Texas, USA.
The neurodevelopmental disorder fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene, which prevents production of the FMRP protein. FMRP modulates the expression and function of a variety of proteins, including voltage-gated ion channels, such as hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders such as FXS.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Physiology and Pharmacology, State University of New York - Downstate Health Sciences University, Brooklyn, NY 11203, USA.
Despite recent advancements in mapping thalamic and cortical projections, the specific organization of intrathalamic and corticothalamic connectivity remains elusive. Current experimental approaches cannot definitively determine whether these connections are arranged in reciprocal (closed-) or non-reciprocal (open-loop) circuits. We developed a biophysically detailed multi-compartmental model of the mouse whisker pathway, built on anatomical and physiological data.
View Article and Find Full Text PDFCell Rep
August 2025
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:
The dorsomedial prefrontal cortex (dmPFC) and basal ganglia (BG) are tightly interconnected through cortico-BG-thalamocortical (CBGT) loops that undergo extensive refinement during postnatal development. While the role of cortical activity in shaping striatal circuit maturation is well established, the extent to which the BG regulate dmPFC development remains unclear. Here, we examined whether early striatal output influences the maturation of dmPFC activity and connectivity.
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