Neuroscience
-
Comparative Study
Anatomical and gene expression mapping of the ventral pallium in a three-dimensional model of developing human brain.
Combining gene expression data with morphological information has revolutionized developmental neuroanatomy in the last decade. Visualization and interpretation of complex images have been crucial to these advances in our understanding of mechanisms underlying early brain development, as most developmental processes are spatially oriented, in topologically invariant patterns that become overtly distorted during brain morphogenesis. It has also become clear that more powerful methodologies are needed to accommodate the increasing volume of data available and the increasingly sophisticated analyses that are required, for example analyzing anatomy and multiple gene expression patterns at individual developmental stages, or identifying and analyzing homologous structures through time and/or between species. ⋯ J Comp Neurol 424:409-438; Puelles L, Martínez S, Martínez-de-la-Torre M, Rubenstein JLR (2004) Gene maps and related histogenetic domains in the forebrain and midbrain. In: The rat nervous system, 3rd ed (Paxinos G, ed), pp 3-25. San Diego: Academic Press].
-
Organotypic hippocampal slice cultures represent a feasible model for studies of cerebral ischemia and the role of ionotropic glutamate receptors in oxygen-glucose deprivation-induced neurodegeneration. New results and a review of existing data are presented in the first part of this paper. The role of glutamate transporters, with special reference to recent results on inhibition of glutamate transporters under normal and energy-failure (ischemia-like) conditions is reviewed in the last part of the paper. ⋯ Adding to this, other results from our laboratory have demonstrated that pre-treatment of the slice cultures with glial cell-line derived neurotrophic factor upregulates glutamate transporters. As a logical, but in some glial cell-line derived neurotrophic factor therapy-related conditions clearly unwanted consequence the susceptibility for oxygen-glucose deprivation-induced glutamate receptor-mediated cell death is increased after glial cell-line derived neurotrophic factor treatment. In summary, we conclude that both ionotropic glutamate receptors and glutamate transporters are involved in oxygen-glucose deprivation-induced necrotic cell death in hippocampal slice cultures, which have proven to be a feasible tool in experimental studies on this topic.
-
Traumatic brain injury causes long-term neurological motor and cognitive deficits, often with limited recovery. The inability of CNS axons to regenerate following traumatic brain injury may be due, in part, to inhibitory molecules associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal outgrowth and sprouting and improves outcome following experimental CNS insults. ⋯ Brain injury significantly increased sprouting from the uninjured corticospinal tract but treatment with monoclonal antibody 11C7 did not further increase the extent of sprouting nor did it alter the extent of CA3 cell damage. Animals treated with 11C7 showed no improvement in neurologic motor deficits but did show significantly improved cognitive function at 4 weeks post-injury when compared with brain-injured, IgG-treated animals. To our knowledge, the present findings are the first to suggest that (1) traumatic brain injury induces axonal sprouting in the corticospinal tract and this sprouting may be independent of myelin-associated inhibitory factors and (2) that post-traumatic inhibition of Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal tract or neuroprotective effects on hippocampal cell loss following experimental traumatic brain injury.
-
Comparative Study
Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs.
Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. ⋯ High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.
-
Comparative Study
Deeply located granule cells and mitral cells undergo apoptosis after transection of the central connections of the main olfactory bulb in the adult rat.
The main olfactory bulb (MOB) is the first relay station of the olfactory system: it receives afferents from sensory neurons and sends efferents to the primary olfactory cortex. The MOB also receives many centrifugal afferents from various regions. Transection of peripheral afferents to the MOB has been reported to induce cell death in granule cells. ⋯ The majority of the degenerating and TUNEL-positive cells were located in the deep, rather than the superficial, GCL. Immunohistochemistry for activated caspase-9 further supported the occurrence of apoptotic cell death in the mitral and deeply located granule cells. These results indicate that not only axotomized mitral cells, but also deeply located granule cells that were not directly injured, underwent apoptosis after transection of the central connections, and suggest that sensitivities to transection of the central connections differ among granule cells according to their depth in the GCL.