Subpopulation Of Local Circuit Neurons Research Articles

Amygdala input monosynaptically innervates parvalbumin immunoreactive local circuit neurons in rat medial prefrontal cortex

The projection from the basolateral nucleus of the amygdala (BLA) conveys information about the affective significance of sensory stimuli to the medial prefrontal cortex (mPFC). By using an anterograde tract-tracing procedure combined with immunocytochemistry and correlated light/electron microscopical examination, labeled BLA afferents to layers 2–6 of the rat mPFC are shown to establish asymmetrical synaptic contacts, not only with dendritic spines (approximately 95.7% of targets innervated), but also with the aspiny dendritic shafts and somata of multipolar parvalbumin immunopositive (PV+) neurons. A population of PV− dendritic shafts was also innervated. Labeled BLA synaptic input to identified PV+ structures occurred in layers 2–6 of mPFC. The results indicate that labeled BLA afferents predominantly contact the spiny processes of presumed pyramidal cells and also provide a direct and specific innervation to a sub-population of local circuit neurons in mPFC containing PV. Since PV+ cells include two significant classes of fast-spiking GABAergic inhibitory interneuron (basket and axo-axonic cells), these novel observations indicate that the amygdalocortical pathway in the rat has the ability to directly influence functionally strategic ‘feed-forward’ inhibitory mechanisms at the first stage of processing amygdalocortical information.

A novel population of calretinin-positive neurons comprises reelin-positive Cajal-Retzius cells in the hippocampal formation of the adult domestic pig.

Calretinin-containing neurons in the hippocampal formation, including the subiculum, presubiculum, parasubiculum, and entorhinal cortex, were visualized with immunocytochemistry. Calretinin immunoreactivity was present exclusively in non-principal cells. The largest immunoreactive cell population was found in the outer half of the molecular layer of the dentate gyrus and in the stratum lacunosum-moleculare of Ammon's horn. A proportion of these cells were also immunoreactive for reelin, a Cajal-Retzius cell marker. Similar calretinin-positive cells were found in the molecular layer of the subicular complex and entorhinal cortex. In the parasubiculum, a few immunoreactive bipolar and multipolar cells could be observed in the superficial and deep pyramidal cell layers. In the entorhinal cortex, bipolar and multipolar calretinin-positive cells were frequent in layer II, and large numbers of multipolar cells in layer V were immunoreactive. Electron microscopic analysis showed that somata of calretinin-positive cells contained either round nuclei with smooth nuclear envelopes or nuclei with multiple deep infoldings. Immunoreactive dendrites were smooth varicose, and the apposing axon terminals formed both symmetric and asymmetric synapses. Zonula adherentia were observed between calretinin-positive dendrites. Calretinin-positive axon terminals formed two types of synapses. Axon terminals with asymmetric synapses were found close to the hippocampal fissure, whereas axon terminals forming symmetric synapses innervated spiny dendrites in both the molecular layer of the dentate gyrus and in stratum lacunosum-moleculare of Ammon's horn. Calretinin-positive axon terminals formed both symmetric and asymmetric synapses with calretinin-positive dendrites. In conclusion, calretinin-positive neurons form two major subpopulations in the adult domestic pig hippocampus: (1) a gamma-aminobutyric acid (GABA)ergic subpopulation of local circuit neurons that innervates distal dendrites of principal cells in both the dentate gyrus and in Ammon's horn; and (2) Cajal-Retzius type cells close to the hippocampal fissure, as well as in the molecular layer of the subicular complex and entorhinal cortex.

Neonatal anandamide treatment results in prolonged mitochondrial damage in the vanilloid receptor type 1-immunoreactive B-type neurons of the rat trigeminal ganglion

Capsaicin acting on the vanilloid type 1 receptor (VR1) excites a subset of primary sensory neurons. Systemic capsaicin treatment of adult or neonatal rats results in selective damage of the B-type neurons in the rat sensory ganglia by causing a long-lasting mitochondrial lesion that has been described in detail in previous studies. The endocannabinoid, anandamide, exhibits an agonist effect on VR1 receptors. The physiological role of anandamide as a VR1 agonist is still uncertain. This study addresses whether high doses of anandamide induce similar ultrastructural changes to those described for capsaicin. The effect of neonatally administered anandamide (1 mg/kg) on neurons of the trigeminal ganglia and the hippocampal formation was examined in the light and electron microscope from the first day after injections to the 20th week after treatment. Anandamide was found to cause mitochondrial damage of the B-type neurons of trigeminal ganglia similar to what has been described for capsaicin. The time course of damage was also comparable. In addition to the cells of the trigeminal ganglia, B-type cells of dorsal root ganglia were also damaged. A-type neurons and satellite glial cells were not affected either in the trigeminal or in the dorsal root ganglia. In the hippocampal formation, where a subpopulation of local circuit neurons is known to contain cannabinoid type 1 (CB1) but not VR1 receptors, anandamide did not cause morphological changes of mitochondria either in the dentate gyrus or in Ammon’s horn. At 3 weeks of age, all VR1-immunoreactive neurons in the trigeminal ganglia of animals treated neonatally with anandamide displayed swollen mitochondria. The results suggest that anandamide, at pharmacologically relevant doses, acts on the VR1 receptor and causes prolonged and selective mitochondrial damage of B-type sensory neurons, as has previously been described for capsaicin.

Local circuit neurons of the prefrontal cortex in schizophrenia: selective increase in the density of calbindin-immunoreactive neurons

Schizophrenia has been reported to be associated with alterations in GABAergic local circuit neurons of the prefrontal cortex. In this study, immunocytochemical techniques and antibodies against the calcium-binding proteins calbindin (CB) and calretinin (CR) were used to determine the laminar distribution and relative density of separate subpopulations of local circuit neurons in prefrontal cortical areas 9 and 46 from five pairs of schizophrenic and control subjects, matched for age, sex, and post-mortem interval. The laminar distribution pattern of CB-immunoreactive local circuit neurons was similar in both schizophrenic and control subjects. In both prefrontal regions, however, the density of CB-labeled neurons was 50–70% greater in schizophrenic subjects compared with control subjects, with cortical layers III and V/VI being preferentially affected. In contrast, the density of CR-IR neurons did not differ significantly between schizophrenic and control subjects. These findings reveal a selective increase in the density of a subpopulation of GABAergic local circuit neurons in the prefrontal cortex. Although other explanations for these observations must be considered, they may be consistent with the hypothesis that gene expression in GABAergic neurons is altered in schizophrenia.

Three distinct subpopulations of GABAergic neurons in rat frontal agranular cortex

GABAergic interneurons in the rat frontal cortex were subdivided on the basis of immunoreactivity for calcium binding proteins, neuropeptides and nitric oxide synthase, using double immunofluorescence and mirror image immunohistochemical methods. The results indicate that in this region of the neocortex there are at least three distinct subpopulations of local circuit neurons. The first subgroup consists of parvalbumin-immunoreactive cells. Those do not contain neuropeptide, calretinin or nitric oxide synthase immunoreactivity. A substantial number of parvalbumin-immunoreactive cells in layer II/III were also immunoreactive for calbindin D 28k. The second subgroup consists of cells immunoreactive for calretinin. Most were usually immunoreactive for vasoactive intestinal polypeptide as well, but a few cells in layer II/III were immunoreactive for one or the other only. Calretinin-immunoreactive cells do not colocalize parvalbumin, somatostatin or nitric oxide synthase, and only a few colocalize calbindin D 28k. The third subgroup consists of cells most of which contain somatostatin, and is entirely separate from the parvalbumin- and calretinin-immunoreactive populations. There was substantial colocalization of somatostatin and calbindin D 28k and of somatostatin and neuropeptide Y. Some somatostatin-immunoreactive cells showed nitric oxide synthase immunoreactivity. All of the populations of immunoreactive cells examined in the present study also showed GABA immunoreactivity. About 10% of calbindin D 28k-immunoreactive cells and all of those strongly stained for calbindin D 28k in layer II/III showed GABA immunoreactivity. Most calbindin D 28k-positive cells in deep layers also showed GABA immunoreactivity. These results support that almost all calbindin D 28k-immunoreactive non-pyramidal cells are probably GABAergic.

Interaction of colocalized neuropeptides: functional significance in the circadian timing system

The suprachiasmatic nucleus (SCN), which appears to act as a circadian clock, contains a subpopulation of local circuit neurons in which vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and gastrin releasing peptide (GRP) are colocalized. To determine whether VIP, PHI, and GRP interact within the SCN to produce a signal important for circadian control, the behavioral and cellular effects of coadministration of these neuropeptides were investigated. Coadministration of VIP, PHI, and GRP within the SCN mimicked the phase-delaying effects of light on circadian control following in vivo microinjection and activated SCN single units recorded in vitro. These behavioral and cellular effects of coadministration of VIP, PHI, and GRP were significantly greater than administration of VIP, PHI, or GRP alone or coadministration of any 2 of these peptides. These data illustrate a new mechanism whereby multiple, colocalized neuropeptides interact in a functionally significant manner, and indicate that the interaction of VIP, PHI, and GRP may be involved in the regulation of circadian rhythms by the SCN.