Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine‐conditioned place preference and associated changes in AMPA receptor binding

Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine‐conditioned place preference (morphine‐CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence. The α7 nAChR antagonist methyllycaconitine (MLA; 4 mg/kg s.c.) had no effect on the acquisition, maintenance, reconsolidation or extinction of morphine‐CPP but selectively attenuated morphine‐primed reinstatement of CPP, in both mice and rats. Reinstatement of morphine‐CPP in mice was accompanied by a selective increase in [3H]‐AMPA binding (but not in [3H]‐MK801 binding) in the ventral hippocampus that was prevented by prior treatment with MLA. Administration of MLA (6.7 μg) directly into the ventral hippocampus of rats prior to a systemic priming dose of morphine abolished reinstatement of morphine‐CPP, whereas MLA delivered into the dorsal hippocampus or prefrontal cortex was without effect. These results suggest that α7 nAChRs in the ventral hippocampus play a specific role in the retrieval of associative drug memories following a period of extinction, making them potential targets for the prevention of relapse

Projections from the brain to the spinal cord in the mouse

The cells that project from the brain to the spinal cord have previously been mapped in a wide range of mammalian species, but have not been comprehensively studied in the mouse. We have mapped these cells in the mouse using retrograde tracing after large unilateral Fluoro-Gold (FG) and horseradish peroxidase (HRP) injections in the C1 and C2 spinal cord segments. We have identified over 30 cell groups that project to the spinal cord, and have confirmed that the pattern of major projections from the cortex, diencephalon, midbrain, and hindbrain in the mouse is typically mammalian, and very similar to that found in the rat. However, we report two novel findings: we found labeled neurons in the precuneiform area (an area which has been associated with the midbrain locomotor center in other species), and the epirubrospinal nucleus. We also found labeled cells in the medial division of central nucleus of the amygdala in a small number of cases. Our findings should be of value to researchers engaged in evaluating the impact of spinal cord injury and other spinal cord pathologies on the centers which give rise to descending pathways

The spinal precerebellar nuclei: Calcium binding proteins and gene expression profile in the mouse

We have localized the spinocerebellar neuron groups in C57BL/6J mice by injecting the retrograde neuronal tracer Fluoro-Gold into the cerebellum and examined the distribution of SMI 32 and the calcium-binding proteins (CBPs), calbindin-D-28K (Cb), calretinin (Cr), and parvalbumin (Pv) in the spinal precerebellar nuclei. The spinal precerebellar neuron clusters identified were the dorsal nucleus, central cervical nucleus, lumbar border precerebellar nucleus, lumbar precerebellar nucleus, and sacral precerebellar nucleus. Some dispersed neurons in the deep dorsal horn and spinal laminae 6–8 also projected to the cerebellum. Cb, Cr, Pv, and SMI 32 were present in all major spinal precerebellar nuclei and Pv was the most commonly observed CBP. A number of genes expressed in hindbrain precerebellar nuclei are also expressed in spinal precerebellar groups, but there were some differences in gene expression profile between the different spinal precerebellar nuclei, pointing to functional diversity amongst them

On-Off Intermittency in Time Series of Spontaneous Paroxysmal Activity in Rats with Genetic Absence Epilepsy

Dynamic behavior of complex neuronal ensembles is a topic comprising a streamline of current researches worldwide. In this article we study the behavior manifested by epileptic brain, in the case of spontaneous non-convulsive paroxysmal activity. For this purpose we analyzed archived long-term recording of paroxysmal activity in animals genetically susceptible to absence epilepsy, namely WAG/Rij rats. We first report that the brain activity alternated between normal states and epilepsy paroxysms is the on-off intermittency phenomenon which has been observed and studied earlier in the different nonlinear systems.Comment: 11 pages, 6 figure

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience

Distribution of raphespinal fibers in the mouse spinal cord

Background: Serotonergic raphespinal neurons and their fibers have been mapped in large mammals, but the non- serotonergic ones have not been studied, especially in the mouse. The present study aimed to investigate the termination pattern of fibers arising from the hindbrain raphe and reticular nuclei which also have serotonergic neurons by injecting the anterograde tracer BDA into them. Results: We found that raphespinal fibers terminate in both the dorsal and ventral horns in addition to lamina 10. There is a shift of the fibers in the ventral horn towards the dorsal and lateral part of the gray matter. Considerable variation in the termination pattern also exists between raphe nuclei with raphe magnus having more fibers terminating in the dorsal horn. Fibers from the adjacent gigantocellular reticular nucleus show similar termination pattern as those from the raphe nuclei with slight difference. Immunofluorescence staining showed that raphespinal fibers were heterogeneous and serotoninergic fibers were present in all laminae but mainly in laminae 1, 2, medial lamina 8, laminae 9 and 10. Surprisingly, immunofluorescence staining on clarified spinal cord tissue revealed that serotoninergic fibers formed bundles regularly in a short distance along the rostrocaudal axis in the medial part of the ventral horn and they extended towards the lateral motor neuron column area. Conclusion: Serotonergic and non-serotonergic fibers arising from the hindbrain raphe and reticular nuclei had similar termination pattern in the mouse spinal cord with subtle difference. The present study provides anatomical foundation for the multiple roles raphe and adjacent reticular nuclei play

Spino-olivary projections in the rat are anatomically separate from postsynaptic dorsal column projections.

The gracile nucleus (GN) and lateral part of rostral dorsal accessory olive (rDAO) are important relays for indirect, postsynaptic dorsal column, and direct ascending pathways, respectively, that terminate as climbing fibers in the "hindlimb-receiving" parts of the C1 and C3 zones in the cerebellar cortex. While the spinal cells of origin of that project to GN and rDAO are from largely separate territories in the spinal cord, previous studies have indicated that there could be an area of overlap between these two populations in the medial dorsal horn. Given the access of these two ascending tracts to sensory (thalamic) versus sensorimotor (precerebellar) pathways, the present study therefore addresses the important question of whether or not individual neurons have the potential to contribute axons to both ascending pathways. A double-fluorescent tracer strategy was used in rats (red Retrobeads and Fluoro-Ruby or green Retrobeads and Fluoro-Emerald) to map the spatial distribution of cells of origin of the two projections in the lumbar spinal cord. The two pathways were found to receive input from almost entirely separate territories within the lumbar cord (levels L3-L5). GN predominantly receives input from lamina IV, while rDAO receives its input from three cell populations: medial laminae V-VI, lateral lamina V, and medial laminae VII-VIII. Cells that had axons that branched to supply both GN and rDAO represented only about 1% of either single-labeled cell population. Overall, the findings therefore suggest functional independence of the two ascending pathways

Dorsal vs. ventral differences in fast Up-state-associated oscillations in the medial prefrontal cortex of the urethane-anesthetized rat.

Cortical slow oscillations (0.1–1 Hz), which may play a role in memory consolidation, are a hallmark of non-rapid eye movement (NREM) sleep and also occur under anesthesia. During slow oscillations the neuronal network generates faster oscillations on the active Up-states and these nested oscillations are particularly prominent in the PFC. In rodents the medial prefrontal cortex (mPFC) consists of several subregions: anterior cingulate cortex (ACC), prelimbic (PrL), infralimbic (IL), and dorsal peduncular cortices (DP). Although each region has a distinct anatomy and function, it is not known whether slow or fast network oscillations differ between subregions in vivo. We have simultaneously recorded slow and fast network oscillations in all four subregions of the rodent mPFC under urethane anesthesia. Slow oscillations were synchronous between the mPFC subregions, and across the hemispheres, with no consistent amplitude difference between subregions. Delta (2–4 Hz) activity showed only small differences between subregions. However, oscillations in the spindle (6–15 Hz)-, beta (20–30 Hz), gamma (30–80 Hz)-, and high-gamma (80–150 Hz)-frequency bands were consistently larger in the dorsal regions (ACC and PrL) compared with ventral regions (IL and DP). In dorsal regions the peak power of spindle, beta, and gamma activity occurred early after onset of the Up-state. In the ventral regions, especially the DP, the oscillatory power in the spindle-, beta-, and gamma-frequency ranges peaked later in the Up-state. These results suggest variations in fast network oscillations within the mPFC that may reflect the different functions and connectivity of these subregions. NEW & NOTEWORTHY We demonstrate, in the urethane-anesthetized rat, that within the medial prefrontal cortex (mPFC) there are clear subregional differences in the fast network oscillations associated with the slow oscillation Up-state. These differences, particularly between the dorsal and ventral subregions of the mPFC, may reflect the different functions and connectivity of these subregions