bioRxiv ScienceSearch

Biology subjects

Micera, S.

Publications and source records attributed to Micera, S..

4 recordsLinked to original sources

Wide-field imaging of cortical neuronal activity with red-shifted functional indicators during motor task execution

Intracellular concentration of free calcium ions in neuronal populations can be longitudinally evaluated by using fluorescent protein indicators, called genetically encoded calcium indicators (GECIs). GECIs with long emission wavelengths are particularly attractive for deep tissue microscopy in vivo, and have the additional advantage of avoiding spectral overlap with commonly used neuronal actuators like Channelrhodopsin.\n\nHere we investigated the performances of selected red-shifted GECIs through an ex vivo characterization and in vivo imaging of cortical mouse activity during motor task execution. Cortical neurons were infected with adeno-associated virus (AAV) expressing one of the red GECI variants (jRCaMP1a, jRCaMP1b, jRGECO1a, jRGECO1b). First we characterized the transfection in terms of extension and intensity using wide-field fluorescence microscopy. Next, we used RCaMP1a to analyse the cortical neuronal activity during motor behaviour. To that end, wide-field fluorescent microscopy and a robotic device for motor control were combined for simultaneous recording of cortical neuronal-activity, force applied and forelimb position during task execution.\n\nOur results show that jRCaMP1a has sufficient sensitivity to monitor in vivo neuronal activity over multiple functional areas, and can be successfully used to perform longitudinal imaging in awake mice.

neuroscience

Optic nerve intraneural stimulation allows selective visual cortex activation

Retinal prostheses have been developed to restore a functional form of vision in patients affected by outer retinal layer dystrophies. Other approaches, namely optic nerve, thalamic, and cortical prostheses are under investigation to expand this toolbox both as clinical devices and as tools for fundamental research. Optic nerve stimulation is attractive since it bypasses the entire retinal network and directly activates nerve fibers. At the same time, it still takes advantage of the high-level information processing occurring downstream in the visual cortex. Here we show that a new intraneural electrode array (OpticSELINE) is effective in inducing the activation of the visual cortex upon electrical stimulation of the optic nerve. We also demonstrate that intraneural optic nerve stimulation induces selective cortical activation patterns depending on the stimulating electrode, thus suggesting that the OpticSELINE possesses spatial selectivity in fiber stimulation. In conclusion, the OpticSELINE can be used both as visual prosthesis for blind patients and as tool to further investigate the effect of the electrical stimulation in the visual system.

bioengineering

A closed-loop hand prosthesis with simultaneous intraneural tactile and position feedback

Current myoelectric prostheses allow upper-limb amputees to regain voluntary motor control of their artificial limb by exploiting residual muscle function in the forearm1. However, the over-reliance on visual cues resulting from a lack of sensory feedback is a common complaint2,3. Recently, several groups have provided tactile feedback in upper-limb amputees by using implanted electrodes4,5,6,7,8, surface nerve stimulation9,10 or sensory substitution11,12. These approaches have led to improved function and prosthesis embodiment4,5,6,7,13,14. Nevertheless, the provided information remains limited to a subset of the rich sensory cues available to healthy individuals. More specifically, proprioception, the sense of limb position and movement, is predominantly absent from current systems. Here we show that sensory substitution based on intraneural stimulation can deliver position feedback in real-time and in conjunction with somatotopic tactile feedback. This approach allowed two trans-radial amputees to regain high and close-to-natural remapped proprioceptive acuity, with a median joint angle reproduction accuracy of 9.1{degrees} and a median threshold to detection of passive movements of 9.5{degrees}, which was compatible with results obtained in healthy subjects15,16,17. The simultaneous delivery of position information and somatotopic tactile feedback allowed both amputees to discriminate object size and compliance with high levels of accuracy (75.5%). These results demonstrate that touch information delivered via somatotopic neural stimulation and position information delivered via sensory substitution can be exploited simultaneously and efficiently by trans-radial amputees. This study paves the way towards more sophisticated bidirectional bionic limbs conveying rich, multimodal sensations.

neuroscience

Rehabilitation Restores Cortical Activation Profiles And Stabilizes Synaptic Contacts After Stroke

Rehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke. Despite its importance, the processes associated with rehabilitative intervention are poorly understood. One of the most challenging experimental goals is to unambiguously link specific circuit changes induced by rehabilitation to improved behavior. Here, we investigate which facets of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We demonstrate the progressive restoration of cortical motor maps and of cortical activity in parallel with the reinforcement of inter-hemispheric connectivity after rehabilitation. Furthermore, we reveal that the increase in vascular density goes along with the stabilization of peri-infarct neural circuitry at synaptic level. The present work provides the first evidences that rehabilitation is sufficient to promote the combined recovery of distinct structural and functional features distinctive of healthy neuronal networks.

neuroscience