Neuroscience
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Horizontal cells form gap junctions with each other in mammalian retina, and lacZ reporter analyses have recently indicated that these cells express the Cx57 gene, which codes for the corresponding gap junctional protein. Using anti-connexin57 antibodies, we detected connexin57 protein in immunoblots of mouse retina, and found punctate immunolabeling of this connexin co-distributed with calbindin-positive horizontal cells in the retinal outer plexiform layer. Double immunofluorescence labeling was conducted to determine the spatial relationships of connexin36, connexin57, the gap junction-associated protein zonula occludens-1 and the photoreceptor ribbon synapse-associated protein bassoon in the outer plexiform layer. ⋯ Connexin57 was often found adjacent to, but not overlapping with, connexin36-positive and zonula occludens-1-positive puncta, and was also located adjacent to bassoon-positive ribbon synapses at rod spherules, and intermingled with such synapses at cone pedicles. These results suggest zonula occludens-1 interaction with connexin36 but not with Cx57 in the outer plexiform layer, and an absence of connexin57/connexin36 heterotypic gap junctional coupling in mouse retina. Further, an arrangement of synaptic contacts within rod spherules is suggested whereby gap junctions between horizontal cell terminals containing connexin57 occur in very close proximity to ribbon synapses formed by rod photoreceptors, as well as in close proximity to Cx36-containing gap junctions between rods and cones.
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Pups are a highly rewarding stimulus for early postpartum rats. Our previous work supports this notion by showing that suckling activates the mesocorticolimbic system in mothers. In the present study, we tested whether development of behavioral sensitization to cocaine before pregnancy affects the neural response to pups during the early postpartum days (PD). ⋯ When tested for maternal behaviors, cocaine-sensitized dams showed significantly faster retrieval of pups without changes in other maternal behaviors such as grouping, crouching and defending the nest. Taken together, the present findings suggest that maternal motivation to retrieve pups was enhanced by repeated cocaine exposure and withdrawal, a result reminiscent of 'cross-sensitization' between the drug and a natural reward. Changes in retrieval behavior in cocaine-sensitized mothers might be associated with a hypo-responsive medial PFC.
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Subsequent to perinatal hypoxia/ischemia there is an increase in the number of neural stem/progenitor cells (NSP) within the subventricular zone (SVZ). Gene expression analyses have implicated Notch signaling in the expansion of these tripotential cells but there are limited data as to which signals are stimulating Notch activation. There is evidence that the leukemia inhibitory factor receptor (LIFR)/gp130 receptor heterodimer induces Notch1 to maintain NSP populations during normal development. ⋯ Whereas CNTF can mimic the effects of LIF in vitro, CNTF expression in the SVZ was unchanged during recovery from H/I. Cumulatively, these data implicate LIF and not CNTF in the expansion of NSPs in the rat SVZ after perinatal brain injury. As both LIF expression and the endogenous regenerative response after brain injury are time-delimited, these findings provide insights into strategies to expand the endogenous pool of NSPs to repopulate the damaged brain.
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Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. ⋯ Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.
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Neuronal competition for action potential initiation sites in a circuit controlling simple learning.
The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of non-associative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. ⋯ A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity.