Electrophysiological studies have long established themselves as reliable methods for assessing the functional state of the brain and spinal cord, the degree of neurodegeneration, and evaluating the effectiveness of therapy. In addition, they can be used to diagnose, predict functional outcomes, and test the effectiveness of therapeutic and rehabilitation programs not only in clinical settings, but also at the preclinical level. Considering the urgent need to develop potential stimulators of neuroregeneration, it seems relevant to obtain objective data when modeling neurological diseases in animals. Thus, in the context of the application of electrophysiological methods, not only the comparison of the basic characteristics of bioelectrical activity of the brain and spinal cord in humans and animals, but also their changes against the background of neurodegenerative and post-traumatic processes are of particular importance. In light of the above, this review will contribute to a better understanding of the results of electrophysiological assessment in neurodegenerative and post-traumatic processes as well as the possibility of translating these methods from model animals to humans.

Background: Adeno-associated viruses (AAVs) are established vectors for efficient gene delivery to the central nervous system (CNS). Increasingly, strategies aim to restrict transduction to specific neuronal subtypes defined by the associated functional properties, thereby enhancing precision and therapeutic potential. Methods: Recombinant AAV9 vectors carrying fluorescent reporters under the control of cytomegalovirus (CMV), human synapsin (hSyn), or homeobox 9 (Hb9) promoters were delivered intrathecally in Wistar rats. Transgene expression was evaluated 7 days post-injection by confocal microscopy. Neurons in laminae VII–X were quantified across cervical, thoracic, lumbar, and sacral spinal cord levels. Statistical analysis was performed using the Kruskal–Wallis test followed by Mann–Whitney U tests with Bonferroni correction. Results: In lamina VII, consistent neuronal expression was mediated by hSyn across all spinal levels, with significantly higher transduction at cervical compared to thoracic and lumbar regions (p < 0.01). CMV and Hb9 showed no detectable tropism for this lamina. In lamina VIII, CMV drove markedly higher expression than hSyn and Hb9, with a 2.8-fold difference at the lumbar level (p < 0.001). In lamina X, CMV expression exceeded hSyn at the lumbar and sacral levels (p < 0.05), while Hb9 showed no activity. In lamina IX, all promoters mediated motoneuron transduction, but only Hb9 restricted expression specifically to motoneuron somata. Notably, CMV induced off-target expression in glial cells. Conclusions: AAV9-mediated expression patterns in the spinal cord are strongly shaped by promoter choice and segmental level. Hb9 provides high motoneuron specificity, hSyn supports broad neuronal activation across laminae VII–X, whereas CMV drives robust but non-specific expression with significant off-target activity. These findings highlight the importance of rational promoter selection for spinal cord gene therapy and strategies aimed at functional recovery in motor system disorders.

Spinal cord injury (SCI) induces persistent locomotor deficits that are closely associated with maladaptive structural plasticity of spinal neuronal circuits. Although motor rehabilitation improves functional outcomes, the cellular substrates underlying rehabilitation-induced recovery remain incompletely understood, particularly in relation to activity-dependent neuromodulation strategies. Here, we investigated how treadmill-based motor training (TMT) and its combination with bioluminescent optogenetic (BL-OG) stimulation of Hb9 (homebox 9)-positive motoneurons and excitatory interneurons selectively modulate microarchitectural plasticity in the injured rat spinal cord. At the level of gross locomotor assessment, Basso, Beattie and Bresnahan (BBB) scores were comparable between the BL-OG and SCI+TMT groups. Although no statistically significant differences in the total score in rung ladder were observed at 28 days post-injury, animals in the BL-OG group showed a tendency toward a higher ratio of successful hindlimb placements, indicating improved step accuracy. BL-OG stimulation was associated with a slightly greater attenuation of SCI-induced spine abnormalities compared to TMT alone, with significant differences between the experimental groups detected specifically in laminae VIII and IX. These lamina-specific alterations in dendritic integration and dendritic spine composition were accompanied by preservation of wisteria floribunda agglutinin WFA-positive perineuronal net (PNN) architecture. Against this background, reduced glypican-4 (GPC-4) expression and attenuated WFA/GPC-4 colocalization were observed in the SCI+BL-OG group relative to SCI in laminae VII–IX, consistent with activity-dependent modulation of PNN-associated synaptic organization in Hb9-positive neuronal populations. Together, these findings indicate that motor rehabilitation and bioluminescent optogenetic stimulation engage distinct but partially overlapping mechanisms of activity-dependent microarchitectural remodeling, preferentially targeting synaptic and perineuronal net-associated substrates rather than inducing large-scale circuit reorganization. Further studies are warranted to elucidate the mechanisms underlying these distinct plasticity profiles.