Principal neurons in the adult cerebral cortex undergo synaptic, dendritic, and spine remodeling in response to different stimuli, and several reports have demonstrated that the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) participates in these plastic processes. However, there is only limited information on the expression of this molecule on interneurons and on its role in the structural plasticity of these cells. We have found that PSA-NCAM is expressed in mature interneurons widely distributed in all the extension of the cerebral cortex and have excluded the expression of this molecule in most principal cells. Although PSA-NCAM expression is generally considered a marker of immature neurons, birth-dating analyses reveal that these interneurons do not have an adult or perinatal origin and that they are generated during embryonic development. PSA-NCAM expressing interneurons show reduced density of perisomatic and peridendritic puncta expressing different synaptic markers and receive less perisomatic synapses, when compared with interneurons lacking this molecule. Moreover, they have reduced dendritic arborization and spine density. These data indicate that PSA-NCAM expression is important for the connectivity of interneurons in the adult cerebral cortex and that its regulation may play an important role in the structural plasticity of inhibitory networks.

Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA-NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar-pyramidal transitional neurons. Most were also immunoreactive for DCX, confirming their immature nature. In agreement with this, detection of PSA-NCAM combined with that of different cell lineage-specific antigens revealed that most PSA-NCAM positive cells did not co-express markers of glial cells or mature neurons. Their time of origin was evaluated by birthdating experiments with halogenated nucleosides performed at different developmental stages and in adulthood. We found that virtually all cells in this paleocortical region, including PSA-NCAM-positive cells, are born during fetal development. In addition, proliferation analyses in adult mice revealed that very few cells were cycling in layer II of the piriform cortex and that none of them was PSA-NCAM-positive. Moreover, we have established conditions to isolate and culture these immature neurons in the adult piriform cortex layer II. We find that although they can survive under certain conditions, they do not proliferate in vitro either. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 748-763, 2016.

Neuronal production persists during adulthood in the dentate gyrus and the olfactory bulb, where substantial numbers of immature neurons can be found. These cells can also be found in the paleocortex layer II of adult rodents, but in this case most of them have been generated during embryogenesis. Recent reports have described the presence of similar cells, with a wider distribution, in the cerebral cortex of adult cats and primates and have suggested that they may develop into interneurons. The objective of this study is to verify this hypothesis and to explore the origin of these immature neurons in adult cats. We have analyzed their distribution using immunohistochemical analysis of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and their phenotype using markers of mature neurons and different interneuronal populations. Additionally, we have explored the origin of these cells administering 5′bromodeoxyuridine (5′BrdU) during adulthood. Immature neurons were widely dispersed in the cerebral cortex layers II and upper III, being specially abundant in the piriform and entorhinal cortices, in the ventral portions of the frontal and temporoparietal lobes, but relatively scarce in dorsal regions, such as the primary visual areas. Only a small fraction of PSA-NCAM expressing cells in layer II expressed the mature neuronal marker NeuN and virtually none of them expressed calcium binding proteins or neuropeptides. By contrast, most, if not all of these cells expressed the transcription factor Tbr-1, specifically expressed by pallium-derived principal neurons, but not CAMKII, a marker of mature excitatory neurons. Absence of PSA-NCAM/5′BrdU colocalization suggests that, as in rats, these cells were not generated during adulthood. Together, these results indicate that immature neurons in the adult cat cerebral cortex layer II are not recently generated and that they may differentiate into principal neurons.

The structure and function of the medial prefrontal cortex (mPFC) is affected in several neuropsychiatric disorders, including schizophrenia and major depression. Recent studies suggest that imbalances between excitatory and inhibitory activity (E/I) may be responsible for this cortical dysfunction and therefore, may underlie the core symptoms of these diseases. This E/I imbalance seems to be correlated with alterations in the plasticity of interneurons but there is still scarce information on the mechanisms that may link these phenomena. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate, because it modulates the neuronal plasticity of interneurons and its expression is altered in schizophrenia and major depression. To address this question, we have developed an in vitro model using mPFC organotypic cultures of transgenic mice displaying fluorescent spiny interneurons. After enzymatic depletion of PSA, the spine density of interneurons, the number of synaptic puncta surrounding pyramidal neuron somata and the E/I ratio were strongly affected. These results point to the polysialylation of NCAM as an important factor in the maintenance of E/I balance and the structural plasticity of interneurons. This may be particularly relevant for better understanding the etiology of schizophrenia and major depression.

MGE cells implanted at the amygdala may control the focal component of temporolimbic seizures. This effect may be mediated by local release of GABA.