Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb, whereas neocortical adult neurogenesis remains controversial. Several occurrences of neocortical adult neurogenesis in injured neocortex were recently reported, suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that can be activated by injury are maintained in the adult brain. However, it is not clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in the neocortical layer 1 of adult rats and observed that their proliferation was highly activated by global forebrain ischemia. Using retrovirus-mediated labeling of layer 1 proliferating cells with membrane-targeted green fluorescent protein, we found that the newly generated neurons were GABAergic and that the neurons were functionally integrated into the neuronal circuitry. Our results suggest that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions.

The primary motor cortex (M1) possesses two intermediate layers upstream of the motor-output layer: layer 2/3 (L2/3) and layer 5a (L5a). Although repetitive training often improves motor performance and movement coding by M1 neuronal ensembles, it is unclear how neuronal activities in L2/3 and L5a are reorganized during motor task learning. We conducted two-photon calcium imaging in mouse M1 during 14 training sessions of a self-initiated lever-pull task. In L2/3, the accuracy of neuronal ensemble prediction of lever trajectory remained unchanged globally, with a subset of individual neurons retaining high prediction accuracy throughout the training period. However, in L5a, the ensemble prediction accuracy steadily improved, and one-third of neurons, including subcortical projection neurons, evolved to contribute substantially to ensemble prediction in the late stage of learning. The L2/3 network may represent coordination of signals from other areas throughout learning, whereas L5a may participate in the evolving network representing well-learned movements.

Vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 show complementary distribution in neocortex; VGLUT1 is expressed mainly in axon terminals of neocortical neurons, whereas VGLUT2 is located chiefly in thalamocortical axon terminals. However, we recently reported a frequent colocalization of VGLUT1 and VGLUT2 at a subset of axon terminals in postnatal developing neocortex. We here quantified the frequency of colocalization between VGLUT1 and VGLUT2 immunoreactivities at single axon terminals by using the correlation coefficient (CC) as an indicator in order to determine the time course and spatial extent of the colocalization during postnatal development of mouse neocortex. The colocalization was more frequent in the primary somatosensory (S1) area than in both the primary visual (V1) and the motor areas; of area S1 cortical layers, colocalization was most evident in layer IV barrels at postnatal day (P) 7 and in adulthood. CC in layer IV showed a peak at P7 in area S1, and at P10 in area V1 though the latter peak was much smaller than the former. These results suggest that thalamocortical axon terminals contained not only VGLUT2 but also VGLUT1, especially at P7-10. Double fluorescence in situ hybridization confirmed coexpression of VGLUT1 and VGLUT2 mRNAs at P7 in the somatosensory thalamic nuclei and later in the thalamic dorsal lateral geniculate nucleus. As VGLUT1 is often used in axon terminals that show synaptic plasticity in adult brain, the present findings suggest that VGLUT1 is used in thalamocortical axons transiently during the postnatal period when plasticity is required.

Myelination increases the conduction velocity in long‐range axons and is prerequisite for many brain functions. Impaired myelin regulation or impairment of myelin itself is frequently associated with deficits in learning and cognition in neurological and psychiatric disorders. However, it has not been revealed what perturbation of neural activity induced by myelin impairment causes learning deficits. Here, we measured neural activity in the motor cortex during motor learning in transgenic mice with a subtle impairment of their myelin. This deficit in myelin impaired motor learning, and was accompanied by a decrease in the amplitude of movement‐related activity and an increase in the frequency of spontaneous activity. Thalamocortical axons showed variability in axonal conduction with a large spread in the timing of postsynaptic cortical responses. Repetitive pairing of forelimb movements with optogenetic stimulation of thalamocortical axon terminals restored motor learning. Thus, myelin regulation helps to maintain the synchrony of cortical spike‐time arrivals through long‐range axons, facilitating the propagation of the information required for learning. Our results revealed the pathological neuronal circuit activity with impaired myelin and suggest the possibility that pairing of noninvasive brain stimulation with relevant behaviors may ameliorate cognitive and behavioral abnormalities in diseases with impaired myelination.