Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex.

The piriform cortex layer II of young-adult rats presents a population of prenatally generated cells, which express immature neuronal markers, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX), and display structural characteristics of immature neurons. The number of PSA-NCAM/DCX expressing cells in this region decreases markedly as age progresses, suggesting that these cells differentiate or die. Since the piriform cortex receives a major input from the olfactory bulb and participates in olfactory information processing, it is possible that the immature neurons in layer II are affected by manipulations of the olfactory bulb or olfactory learning. It is not known whether these cells can be induced to differentiate and, if so, what would be their fate. In order to address these questions, we have performed unilateral olfactory bulbectomy (OBX) and an olfactory learning paradigm (taste-potentiated odor aversion, TPOA), in young-adult rats and have studied the expression of different mature and immature neuronal markers, as well as the presence of cell death. We have found that 14 h after OBX there was a dramatic decrease in the number of both PSA-NCAM and DCX expressing cells in piriform cortex layer II, whereas that of cells expressing NeuN, a mature neuronal marker, increased. By contrast, the number of cells expressing glutamate decarboxylase, isoform 67 (GAD67), a marker for interneurons, decreased slightly. Additionally, we have not found evidence of numbers of dying cells high enough to justify the disappearance of immature neurons. Analysis of animals subjected to TPOA revealed that this paradigm does not affect PSA-NCAM expressing cells. Our results strongly suggest that OBX can induce the maturation of immature neurons in the piriform cortex layer II and that these cells do not become interneurons. By contrast, these cells do not seem to play a crucial role in olfactory memory.

"Arrested development". Immature, but not recently generated, neurons in the adult brain.

After the division of neuronal precursors, many of the newly generated cells become immature neurons, which migrate to their final destination in the nervous system, extend neurites and make appropriate connections. For most neurons these events occur in a narrow time window and, once in their definitive location, they immediately start the final stages of their differentiation program, remaining immature only for a short time. The main objective of this review is to present and discuss recent data on a peculiar population of cells in the adult brain, which retain an immature neuronal phenotype for an unusually prolonged time. We review and discuss recent evidence on the temporal and spatial origin of these cells, their distribution in rodents and other mammals, their structure and neurochemical phenotype, and their putative fate and function. The review is mainly focused on the population of immature neurons located in the layer II of certain cortical regions, but we will also describe similar populations found in other regions of the peripheral and central nervous systems.

Effects of chronic fluoxetine treatment on the rat somatosensory cortex: activation and induction of neuronal structural plasticity.

Recent hypotheses support the idea that disruption of normal neuronal plasticity mechanisms underlies depression and other psychiatric disorders, and that antidepressant treatment may counteract these changes. In a previous report we found that chronic fluoxetine treatment increases the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule involved in neuronal structural plasticity, in the somatosensory cortex. In the present study we intended to find whether, in fact, cell activation and neuronal structural remodeling occur in parallel to changes in the expression of this molecule. Using immunohistochemistry, we found that chronic fluoxetine treatment caused an increase in the expression of the early expression gene c-fos. Golgi staining revealed that this treatment also increased spine density in the principal apical dendrite of pyramidal neurons. These results indicate that, apart from the medial prefrontal cortex or the hippocampus, other cortical regions can respond to chronic antidepressant treatment undergoing neuronal structural plasticity.

Chronic antidepressant treatment induces contrasting patterns of synaptophysin and PSA-NCAM expression in different regions of the adult rat telencephalon.

Structural modifications occur in the brain of severely depressed patients and they can be reversed by antidepressant treatment. Some of these changes do not occur in the same direction in different regions, such as the medial prefrontal cortex, the hippocampus or the amygdala. Differential structural plasticity also occurs in animal models of depression and it is also prevented by antidepressants. In order to know whether chronic fluoxetine treatment induces differential neuronal structural plasticity in rats, we have analyzed the expression of synaptophysin, a protein considered a marker of synaptic density, and the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule involved in neurite and synaptic remodeling. Chronic fluoxetine treatment increases synaptophysin and PSA-NCAM expression in the medial prefrontal cortex and decreases them in the amygdala. The expression of these molecules is also affected in the entorhinal, the visual and the somatosensory cortices.

N-methyl-d-aspartate receptor expression during adult neurogenesis in the rat dentate gyrus.

N-methyl-d-aspartate (NMDA) receptors play a crucial role in the regulation of neuronal development during embryogenesis and they also regulate the rate of neurogenesis and proliferation in the adult dentate gyrus. However, the mechanism by which they influence these processes is not fully understood. NMDA receptors seem to be functional in hippocampal precursor cells and recently generated granule neurons, although there is no anatomical correlate of these physiological observations. We have analyzed the expression of the NMDA receptor subunits NR1 and NR2B in precursor cells and recently generated granule neurons of the adult rat dentate gyrus, using 5'bromodeoxyuridine, green fluorescent protein-retrovirus and immunohistochemistry. Our results indicate that NR1 and NR2B are expressed in some proliferating cells of the adult subgranular zone. These receptors are absent from transiently amplifying progenitors (type 2-3 cells) but they are found in glial fibrillar acidic protein expressing cells in the subgranular zone, suggesting its presence in bipotential (type-1) precursor cells. NR1 and NR2B are rarely found in granule cells younger than 60 h. By contrast, many granule cells generated 14 days before killing express both NMDA receptor subunits. These results demonstrate that adult hippocampal neurogenesis may be regulated by NMDA receptors present in precursor cells and in differentiating granule neurons, although these receptors are probably not located on synapses. However, an indirect effect through NMDA receptors located in other cell types should not be excluded.

PSA-NCAM expression in the rat medial prefrontal cortex.

The rat medial prefrontal cortex, an area considered homologous to the human prefrontal cortex, is a region in which neuronal structural plasticity has been described during adulthood. Some plastic processes such as neurite outgrowth and synaptogenesis are known to be regulated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). Since PSA-NCAM is present in regions of the adult CNS which are undergoing structural remodeling, such as the hypothalamus or the hippocampus, we have analyzed the expression of this molecule in the medial prefrontal cortex of adult rats using immunohistochemistry. PSA-NCAM immunoreactivity was found both in cell bodies and in the neuropil of the three divisions of the medial prefrontal cortex. All cell somata expressing PSA-NCAM corresponded to neurons and 5' bromodeoxyuridine labeling after long survival times demonstrated that these neurons were not recently generated. Many of these PSA-NCAM immunoreactive neurons in the medial prefrontal cortex could be classified as interneurons on the basis of their morphology and glutamate decarboxylase, isoform 67 expression. Some of the PSA-NCAM immunoreactive neurons also expressed somatostatin, neuropeptide Y and calbindin-D28K. By contrast, pyramidal neurons in this cortical region did not appear to express PSA-NCAM. However, some of these principal neurons appeared surrounded by PSA-NCAM immunoreactive puncta. Some of these puncta co-expressed synaptophysin, suggesting the presence of synapses. Since the etiology of some psychiatric disorders has been related to alterations in medial prefrontal cortex structural plasticity, the study of PSA-NCAM expression in this region may open a new approach to the pathophysiology of these mental disorders.