SEMINARIO: The role of higher-order thalamocortical input in cortical synaptic plasticity. Anthony Holtmaat. Department of Basic Neurosciences,Geneva Neuroscience Center. University of Geneva, Suiza.

Seminario:  The role of higher-order thalamocortical input in cortical synaptic plasticity.

Conferenciante: Anthony Holtmaat. Department of Basic Neurosciences,Geneva Neuroscience Center. University of Geneva, Suiza. (Curriculum, ver PDF adjunto).

Resumen: Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons, possibly mediated by long-term potentiation (LTP) of synapses. We have previously shown in the mouse somatosensory cortex (S1) that sensory-driven LTP in layer (L) 2/3 pyramidal neurons is dependent on higher order thalamic projections from the posteromedial nucleus (POm), which is thought to convey contextual information from various cortical regions integrated with sensory input.  Here, we followed up by dissecting the cortical microcircuitry underlying this form of LTP, and by characterizing POm-originating afferent activity during whisker sensory discrimination learning. We found that repeated pairing of POm thalamocortical and intracortical pathway activity in brain slices induces NMDAr-dependent LTP of the L2/3 synapses that are driven by the intracortical pathway. In addition, we found that the simultaneous activation of the two pathways recruits activity of vasoactive intestinal peptide (VIP) interneurons, whereas it reduces the activity of somatostatin (SST) interneurons. VIP interneuron-mediated inhibition of SST interneurons has been established as a motif for the disinhibition of pyramidal neurons. Selective expression of the hM4Di receptor (an inhibitory Designer Receptor Exclusively Activated by Designer Drugs - DREADD) in these two interneuron subtypes, we found that activation of this disinhibitory microcircuit motif by higher-order thalamic inputs indispensable for eliciting LTP. This suggests that in vivo, these projections may help modifying the strength of synaptic circuits that process first-order sensory information in S1. To characterize the relationship between higher-order thalamic activity and cortical plasticity during learning in vivo, we adapted a perceptual learning paradigm in which head-fixed mice have to discriminate two types of textures in order to obtain a reward. POm axons or L2/3 pyramidal neurons labeled with the genetically encoded calcium indicator GCaMP6s were imaged during the acquisition of this task as well as the subsequent learning of a new discrimination rule. We found that a subpopulation of the POm axons stably represent textures, even upon a texture-rule change, whereas a relatively large fraction of the L2/3 neurons re-tune their selectivity to the texture that is newly associated with the reward. Altogether, our data suggest that higher-order thalamic input shapes synaptic circuits in S1 that may be important for processing of sensory input and texture discrimination.

Bibliografía recomendada:

Roelfsema PR, Holtmaat A (2018) Control of synaptic plasticity in deep cortical networks.

Nat. Rev. Neurosci. 19: 166-180. Review

Williams L, Holtmaat A. (2018) Higher-order thalamocortical inputs gate synaptic long-term

potentiation via disinhibiton. bioRxiv. https://doi.org/10.1101/281477

Fecha y hora: Viernes, 18 de enero de 2019, 13 h.

Lugar: Seminario IV.

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