Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats.

While reward-dependent facilitation of phasic dopamine signaling is well documented at both the cell bodies and terminals, little is known regarding fast dopamine transmission under aversive conditions. Exposure to aggressive confrontation is extremely aversive and stressful for many species including rats. The present study used fast-scan cyclic voltammetry and multiunit recording to determine if aggressive encounters and subsequent social defeat affect burst firing of ventral tegmental area (VTA) dopamine neurons and accumbal dopamine transients in defeated rats. Significant increases in the frequency of transient dopamine release were observed during interactions with an aggressive rat but not with a familiar cage mate. In agreement with voltammetric results, significant increases in burst frequency were detected in the VTA dopamine firing patterns during an aggressive confrontation; however, the number of spikes per burst remained unchanged. We found that neurons with lower burst rates under home cage conditions did not switch from nonbursting to bursting types, while neurons with higher burst levels showed amplified increases in bursting. This study demonstrates for the first time that aggressive confrontations in defeated rats are associated with increases in phasic dopamine transmission in the mesolimbic pathway.

Effects of restraint and haloperidol on sensory gating in the midbrain of awake rats.

Deficits in sensory processing have been reported to be associated with an array of neuropsychiatric disorders including schizophrenia. Auditory sensory gating paradigms have been routinely used to test the integrity of inhibitory circuits hypothesized to filter sensory information. Abnormal dopaminergic neurotransmission has been implicated in the expression of schizophrenic symptoms. The aim of this study was to determine if inhibitory gating in response to paired auditory stimuli would occur in putative dopaminergic and non-dopaminergic midbrain neurons. A further goal of this study was to determine if restraint, a classic model of stress known to increase extracellular dopamine levels, and systemic haloperidol injections affected inhibitory mechanisms involved in sensory gating. Neural activity in the rat midbrain was recorded across paired auditory stimuli (first auditory stimulus (S1) and second auditory stimulus (S2)) under resting conditions, during restraint and after systemic haloperidol injections. Under resting conditions, a subset of putative GABA neurons showed fast, gated, short latency responses while putative dopamine neurons showed long, slow responses that were inhibitory and ungated. During restraint, gated responses in putative GABAergic neurons were decreased (increased S2/S1 or ratio of test to conditioning (T/C)) by reducing the response amplitude to S1. Systemic haloperidol decreased the T/C ratio by preferentially increasing response amplitude to S1. The results from this study suggest that individual neurons encode discrete components of the auditory sensory gating paradigm, that phasic midbrain GABAergic responses to S1 may trigger subsequent inhibitory filtering processes, and that these GABAergic responses are sensitive to restraint and systemic haloperidol.

Distribution of the calcium-binding proteins calbindin D-28K and parvalbumin in the superior colliculus of adult and neonatal cat and rhesus monkey.

The distribution of the calcium-binding proteins calbindin D-28K and parvalbumin was examined in newborn and adult superior colliculus of cat and rhesus monkey using immunohistochemical techniques. In adult animals of both species, calbindin-immunoreactive neurons had a three-tiered arrangement: one band was present in the upper aspects of the superficial laminae, a second in the intermediate laminae, and a third in the deep laminae. The intermediate tier was less obvious in the monkey, whereas the deep tier was less pronounced in the cat. Parvalbumin-immunoreactive neurons had a complementary distribution to calbindin-immunoreactive neurons within these laminae in both species, although the segregation of calbindin immunoreactivity and parvalbumin immunoreactivity in the superficial laminae was not as precise in the monkey as it was in the cat. At birth, calbindin immunoreactivity in the newborns of both species was remarkably mature, with its three-tiered distribution clearly evident. By contrast, parvalbumin immunoreactivity was distinctly different in the newborn cat than in the newborn monkey: whereas parvalbumin immunoreactivity in the newborn monkey was already very similar to its adult-like pattern, the pattern in the newborn cat was quite immature. The superficial laminae of the newborn cat were virtually devoid of parvalbumin immunoreactivity, and, although the intermediate laminae displayed robust parvalbumin-immunoreactive neuropil, comparatively fewer parvalbumin-immunoreactive neurons were observed. Conspicuously few in number were the large multipolar neurons in the intermediate laminae, which give rise to the descending efferents to the brainstem. However, parvalbumin-immunoreactive neurons were present within the deep laminae, suggesting a ventral-to-dorsal maturational gradient in parvalbumin expression that parallels the ventral-to-dorsal gradient of neurogenesis. The differences in parvalbumin immunoreactivity observed between these two species at parturition are consistent with the advanced visual and visuomotor capabilities of the newborn monkey and the absence of visually related behaviors in the newborn cat.

Tenascin-C lines the migratory pathways of avian primordial germ cells and hematopoietic progenitor cells.

Tenascin-C is a large hexameric extracellular matrix glycoprotein associated with epithelial-mesenchymal interactions, connective tissue development, and the formation of the central nervous system. Tenascin-C also lines the pathways followed by migrating avian neural crest cells, although its role in neural crest morphogenesis remains unclear. In vitro, tenascin-C interferes with cell-fibronectin interactions, and promotes the motility of many cell types including the neural crest. To determine if tenascin-C is a consistent component of matrices through which invasive embryonic cells migrate, we have investigated if tenascin-C is associated with 2 additional populations of motile, embryonic cells: primordial germ cells and hematopoietic progenitor cells. We have found that HNK-1, a monoclonal antibody used as a marker of neural crest, also stains avian primordial germ cells. Double-label immunohistochemistry reveals that tenascin-C is found in the mesenchyme adjacent to the ventral half of the dorsal aorta where the primordial germ cells penetrate the vessel wall, and both tenascin-C and fibronectin are present in the extracellular matrix through which the primordial germ cells migrate to reach the genital ridges. Unlike fibronectin, which is found throughout the splanchnic mesoderm, tenascin-C is concentrated in the proximal part of the splanchnic region where the primordial germ cells are concentrated. In embryos where the gonadal anlagen are surgically removed before the primordial germ cells leave the bloodstream, ectopic primordial germ cells were found exclusively in head and trunk mesenchyme containing tenascin-C. Like primordial germ cells, a subset of hematopoietic progenitor cells migrate through the mesenchyme ventral to the dorsal aorta where they form hematopoietic clusters. Others bud directly into the lumen of the aorta. Anti-tenascin-C stains the mesenchyme surrounding the migrating cells as well as the basal surfaces of the cells that appear to be budding into the lumen. In situ hybridization with a tenascin-C-specific cDNA probe shows that the major sources of the tenascin-C mRNA in this region are the hematopoietic progenitor cells themselves as well as the cells in the wall of the ventral aorta. mRNAs encoding 3 major splice variants of tenascin-C were identified by reverse transcriptase polymerase chain reaction (PCR) in the embryonic aorta and adjacent mesenchyme dissected from both the region of primordial germ cell and hematopoietic precursor cell migration. These experiments indicate that tenascin-C is a component of the migratory environment for many motile cells in the early embryo, where it has the potential to mediate cell-fibronectin interactions.