Somatotopically inappropriate projections from thalamocortical neurons to the SI cortex of the cat demonstrated by the use of intracortical microstimulation

Single thalamocortical neurons with receptive fields on the toes were antidromically activated by the passage of 300-microseconds, 0.5- to 10-microA pulses through glass micropipette electrodes placed within somatotopically identified regions of the digit representation of the cat first somatosensory (SI) cortex. The somatotopy of the cortex was determined using recordings from single cortical neurons (see "Methods"), and the positions of the all tracks were marked on an enlarged photograph of the postcruciate cortex. In two of the three protocols, a very precise map of the boundary between two adjacent toes was produced prior to attempting intracortical microstimulation. Slopes of the threshold-distance curves at the sites of the lowest recorded thresholds were on the order of 0.8 microA/10 micron. This value, together with information on the anatomy of the cortical arborizations of thalamocortical neurons (Landry and Deschenes, 1981), suggested that currents of 2 and 5 microA would not activate the cortical processes of thalamocortical neurons at distances greater than 50 and 90 microns, respectively. With currents below 5 microA, thalamocortical neurons could be antidromically activated at a number of sites at depths between 340 and 930 microns (layer IV and upper layer III) and between 1,050 and 1,460 microns (layer VI). A total of 13 thalamocortical neurons could be antidromically activated using current pulses of between 0.8 and 5.0 microA, from within tracks at tangential distances of 250-830 microns from the nearest track through the somatotopically appropriate region. Within somatotopically inappropriate regions, cortical neurons frequently had receptive fields on a toe adjacent to that bearing the receptive field of the thalamic neuron(s) under study. The possible relationship of somatotopically inappropriate projections to the reorganization of cortical somatotopy following digit amputation, paw amputation, and nerve section is discussed

Assessing Perturbations to Neural Spiking Response Dynamics Caused by Electrical Microstimulation

This study assesses the feasibility of latent factor analysis via dynamical systems (LFADS) for evaluating differences in the observed spiking response dynamics imposed by two electrical microstimulation regimes in awake rats. LFADS is a recently-developed deep learning method that uses stimulus-aligned neural spiking data to determine the initial neural state of each trial, as well as infer a set of time-dependent perturbations to the learned neural dynamics within trials. We show that time-dependent perturbations inferred by an LFADS model trained on spikes from trials on a single session can distinguish between different stimulation conditions. Furthermore, we use these data to exemplify how LFADS inferences track the evolution of stimulus-related spiking responses during chronic microstimulation experiments

Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery

We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery

Differential Effects of Open- and Closed-Loop Intracortical Microstimulation on Firing Patterns of Neurons in Distant Cortical Areas

Intracortical microstimulation can be used successfully to modulate neuronal activity. Activity-dependent stimulation (ADS), in which action potentials recorded extracellularly from a single neuron are used to trigger stimulation at another cortical location (closed-loop), is an effective treatment for behavioral recovery after brain lesion, but the related neurophysiological changes are still not clear. Here, we investigated the ability of ADS and random stimulation (RS) to alter firing patterns of distant cortical locations. We recorded 591 neuronal units from 23 Long-Evan healthy anesthetized rats. Stimulation was delivered to either forelimb or barrel field somatosensory cortex, using either RS or ADS triggered from spikes recorded in the rostral forelimb area (RFA). Both RS and ADS stimulation protocols rapidly altered spike firing within RFA compared with no stimulation. We observed increase in firing rates and change of spike patterns. ADS was more effective than RS in increasing evoked spikes during the stimulation periods, by producing a reliable, progressive increase in stimulus-related activity over time and an increased coupling of the trigger channel with the network. These results are critical for understanding the efficacy of closed-loop electrical microstimulation protocols in altering activity patterns in interconnected brain networks, thus modulating cortical state and functional connectivity