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Teichert, M.

Publications and source records attributed to Teichert, M..

6 recordsLinked to original sources

Harnessing early multimodal motor training to drive motor recovery and brain-wide structural reorganization after stroke

Stroke survivors often suffer from severe motor impairments, highlighting the critical need for effective rehabilitation strategies. In experimental models, extensive task-specific motor training within the first few weeks post-stroke significantly mitigates motor deficits. However, whether more multimodal motor training approaches after stroke can restore task-specific performance in non-trained motor tasks remains largely unknown. Additionally, while stroke itself triggers structural brain reorganization, the influence of early multimodal motor training on this process remains unclear. Here, we employed T2-weighted MRI to investigate brain region-specific volumetric changes over eight weeks in rats subjected to stroke and subsequent early multimodal motor training. We found that this combination not only facilitated task-specific motor function recovery, but also induced dramatic, multi-region, brain-wide volumetric changes. Specifically, over 80 locations within 50 distinct brain regions across both hemispheres exhibited substantial volumetric alterations in a predominantly bilateral symmetric pattern. In contrast, stroke or training alone resulted in changes in 8-15 locations within 7-13 brain regions, with stroke alone primarily affecting the infarcted hemisphere. Analysis of temporal volume changes revealed two distinct trajectories in post-stroke trained rats: one of initial swelling followed by shrinkage, and another of initial shrinkage followed by swelling, suggesting an early and delayed motor learning period. Overall, our findings demonstrate that multimodal motor training early after stroke effectively restores task-specific motor function and profoundly reshapes brain structure on a brain-wide scale, offering vital insights for developing optimized rehabilitation protocols to maximize recovery in stroke patients.

neuroscience↗

Layer 6 corticocortical cells dominate the anatomical organization of intra and interhemispheric feedback

The mouse neocortex contains at least ninety distinctly defined yet interconnected areas that are symmetrically located across the two hemispheres. Determining the logic of this long range circuitry is necessary for understanding how inter-areal integration enables high level brain function involving multiple sensory, motor and cognitive processes. To address this we have performed a systematic anatomical analysis of the areal and laminar organization of the ipsilateral and contralateral cortical projection onto the primary visual (VISp), primary somatosensory barrel field (SSp-bfd) and primary motor (MOp) cortices. The resultant input maps reveal that although the ipsilateral hemisphere is the primary source of cortical input, there is substantial bilateral symmetry regarding the relative contribution and areal identity of contralateral input. Laminar analysis of these input areas show that excitatory Layer 6 corticocortical cells (L6 CCs) are a major projection pathway from both within and across the two hemispheres. Based on cortical hierarchy analysis that compares the relative contribution of inputs from supra-(feedforward) and infra-granular (feedback) layers, we find that contra-hemispheric projections reflect a dominant feedback organization compared to their ipsi-cortical counterpart. The magnitude of the interhemispheric difference in hierarchy was largest for sensory and motor projection areas compared to frontal, medial or lateral brain areas and can be explained by a proportional increase in input from L6 neurons. L6 CCs therefore not only mediate long-range cortical communication but also reflect its inherent feedback organization.

neuroscience↗

A primary sensory cortical interareal feedforward inhibitory circuit for tacto-visual integration

Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems might combine such information. Here in mice we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a subarea of primary visual cortex (VISp) whose visual space covers the whisker search space. This is mediated by local fast spiking interneurons that receive a direct cortico-cortical input predominantly from layer 6 of the primary somatosensory barrel cortex (SSp-bfd). These data demonstrate functional convergence within and between two primary sensory cortical areas for multisensory object detection and recognition.

neuroscience↗

Social hierarchy regulates ocular dominance plasticity in adult male mice.

We here show that social rank, as assessed by competition for a running wheel, influences ocular dominance plasticity in adult male mice. Dominant animals showed a clear ocular dominance shift after four days of MD, whereas their submissive cage mates did not. NMDA receptor activation, reduced GABA inhibition, and serotonin transmission were necessary for this plasticity, but not sufficient to explain the difference between dominant and submissive animals. In contrast, prefrontal dopamine concentration was higher in dominant than submissive mice, and systemic manipulation of dopamine transmission bidirectionally changed ocular dominance plasticity. Thus, we could show that a social hierarchical relationship influences ocular dominance plasticity in the visual cortex via higher-order cortices, most likely the medial prefrontal cortex. Further studies will be needed to elucidate the precise mechanisms by which this regulation takes place.

neuroscience↗

Cross-modal restoration of juvenile-like ocular dominance plasticity after increasing GABAergic inhibition

In juvenile and \"young adult\" mice monocular deprivation (MD) shifts the ocular dominance (OD) of binocular neurons in the primary visual cortex (V1) away from the deprived eye. However, OD plasticity is completely absent in mice older than 110 days, but can be reactivated by treatments which decrease GABA levels in V1. Typically, these OD shifts can be prevented by increasing GABAergic transmission with diazepam. We could recently demonstrate that both bilateral whisker and auditory deprivation (WD, AD), can also restore OD plasticity in mice older than 110 days, since MD for 7 days in WD mice caused a potentiation of V1 input through the ipsilateral (open) eye, the characteristic feature of OD plasticity of \"young adult\" mice. Here we examined whether WD for 7 days also decreases GABA levels. For this, we performed post mortem HPLC analysis of V1 tissue. Indeed, we found that WD significantly decreased GABA levels in V1. Surprisingly, enhancing GABAergic inhibition by diazepam did not abolish OD shifts in WD mice, as revealed by repeated intrinsic signal imaging. On the contrary, this treatment led to a depression of V1 input through the previously closed contralateral eye, the characteristic signature of OD plasticity in juvenile mice during the critical period. Interestingly, the same result was obtained after AD. Taken together, these results suggest that cross-modally restored OD plasticity does not only depend on reduction of GABA levels in V1, but also requires other, so far unknown mechanisms.

neuroscience↗

Visual deprivation independent shift of ocular dominance induced by cross-modal plasticity

There is convincing evidence that the deprivation of one sense can lead to adaptive neuronal changes in the spared primary sensory cortices. However, the repercussions of late-onset sensory deprivations on functionality of the remaining sensory cortices are poorly understood. Using repeated intrinsic signal imaging we investigated the effects of whisker or auditory deprivation (WD or AD, respectively) on responsiveness of the binocular primary visual cortex (V1) in fully adult mice. The binocular zone of mice is innervated by both eyes, with the contralateral eye always dominating V1 input over ipsilateral eye input, the normal ocular dominance (OD) ratio. Strikingly, we found that 3 days after WD or AD there was a transient shift of OD, which was mediated by a potentiation of V1 input through the ipsilateral eye. This cross-modal effect was accompanied by strengthening of V1 layer 4 synapses, required visual experience through the ipsilateral eye and was mediated by an increase of the excitation/inhibition ratio in V1. Finally, we demonstrate that both WD and AD induced a long-lasting improvement of visual performance. Our data provide evidence that the deprivation of a non-visual sensory modality cross-modally induces experience dependent V1 plasticity and improves visual behavior, even in adult mice.

neuroscience↗