Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits

Recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional “remapping” occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel. Using in vivo calcium imaging to longitudinally record sensory-evoked activity under light anesthesia, we did not find any increase in the number of C1 whisker-responsive neurons in the adjacent, spared D3 barrel after stroke. To promote plasticity after stroke, we also plucked all whiskers except C1 (forced use therapy). This led to an increase in the reliability of sensory-evoked responses in C1 whisker-responsive neurons but did not increase the number of C1 whisker-responsive neurons in spared surround barrels over baseline levels. Our results argue against remapping of functionality after barrel cortex stroke, but support a circuit-based mechanism for how rehabilitation may improve recovery.

Plasticity after cortical stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits

Functional recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. This “remapping” hypothesis is based on human brain mapping studies showing apparent reorganization of cortical sensorimotor maps and animal studies documenting molecular and structural changes that could support circuit rewiring. However, definitive evidence of remapping is lacking, and other studies have suggested that maladaptive plasticity mechanisms, such as enhanced inhibition in peri-infarct cortex, might actually limit plasticity after stroke. Here we sought to directly test whether neurons can change their response selectivity after a stroke that destroys a single barrel (C1) within mouse primary somatosensory cortex. Using multimodal in vivo imaging approaches, including two-photon calcium imaging to longitudinally record sensory-evoked activity in peri-infarct cortex before and after stroke, we found no evidence to support the remapping hypothesis. In an attempt to promote plasticity via rehabilitation, we also tested the effects of forced use therapy by plucking all whiskers except the C1 whisker. Again, we failed to detect an increase in the number of C1 whisker-responsive neurons in surrounding barrels even 2 months after stroke. Instead, we found that forced use therapy potentiated sensory-evoked responses in a pool of surviving neurons that were already C1 whisker responsive by significantly increasing the reliability of their responses. Together, our results argue against the long-held theory of functional remapping after stroke, but support a plausible circuit-based mechanism for how rehabilitation may improve recovery of function.

Neuron-class specific responses govern adaptive remodeling of myelination in the neocortex

Myelination plasticity plays a critical role in neurological function, including learning and memory. However, it is unknown whether this plasticity is enacted through uniform changes across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable fine-tuning of adaptive circuit responses. We performed in vivo two-photon imaging to investigate the dynamics of myelin sheaths along single axons of both excitatory callosal projection neurons and inhibitory parvalbumin+ interneurons in layer 2/3 of adult mouse visual cortex. We find that both neuron types show dynamic, homeostatic myelin remodeling under normal vision. However, monocular deprivation results in experience-dependent adaptive myelin remodeling only in parvalbumin+ interneurons, but not in callosal projection neurons. Monocular deprivation induces an initial increase in elongation events in myelin segments of parvalbumin+ interneurons, followed by a contraction phase affecting a separate cohort of segments. Sensory experience does not alter the generation rate of new myelinating oligodendrocytes, but can recruit pre-existing oligodendrocytes to generate new myelin sheaths. Parvalbumin+ interneurons also show a concomitant increase in axonal branch tip dynamics independent from myelination events. These findings suggest that adaptive myelination is part of a coordinated suite of circuit reconfiguration processes, and demonstrate that distinct classes of neocortical neurons individualize adaptive remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.

Adaptive Circuit Dynamics Across Human Cortex During Evidence Accumulation in Changing Environments

Many decisions under uncertainty entail the temporal accumulation of evidence that informs about the state of the environment. When environments are subject to hidden changes in their state, maximizing accuracy and reward requires non-linear accumulation of the evidence. How this adaptive, non-linear computation is realized in the brain is unknown. We analyzed human behavior and cortical population activity (measured with magnetoencephalography) recorded during visual evidence accumulation in a changing environment. Behavior and decision-related activity in cortical regions involved in action planning exhibited hallmarks of adaptive evidence accumulation, which could also be implemented by a recurrent cortical microcircuit. Decision dynamics in action-encoding parietal and frontal regions were mirrored in a frequency-specific modulation of the state of visual cortex that depended on pupil-linked arousal and the expected probability of change. These findings link normative decision computations to recurrent cortical circuit dynamics and highlight the adaptive nature of decision-related feedback to sensory cortex.

An adaptive negative capacitance circuit for enhanced performance and robustness of piezoelectric shunt damping

Piezoelectric shunt damping is investigated as one possible solution for improving the vibroacoustic behavior of noise-prone lightweight structures. The negative capacitance shunt circuit appears to be the best choice due to its broadband damping effect. Usually, it is built from analog electronic components, such as operational amplifiers, resistors, and capacitors. In terms of damping efficiency and the vibroacoustic behavior of the circuit, the capacitance ratio between the negative capacitance and the inherent capacitance of the piezoelectric transducer is of major concern. For laboratory setups, this ratio may be adjusted manually, but for real applications, this is not suitable due to a lack of damping or the risk of instability of the circuit. Therefore, an improved approach is presented in this article, where a concept for an adaptive negative capacitance circuit is presented. An electronically tunable resistor is used to change the value of the negative capacitance to the best fit for the present conditions. Adjustment laws for the ideal value of this resistor are derived from the transfer function of the whole circuit. Finally, a prototype board is designed and experimentally tested at a beam structure. It can be shown that the adaptive circuit allows a tighter adjustment to the edge of stability resulting in higher damping or, in the case of too high vibration amplitudes, prevents the output voltage from saturating.