BackgroundThe mammalian amygdala is composed of two primary functional subdivisions, classified according to whether the major output projection of each nucleus is excitatory or inhibitory. The posterior dorsal and ventral subdivisions of the medial amygdala, which primarily contain inhibitory output neurons, modulate specific aspects of innate socio-sexual and aggressive behaviors. However, the development of the neuronal diversity of this complex and important structure remains to be fully elucidated.ResultsUsing a combination of genetic fate-mapping and loss-of-function analyses, we examined the contribution and function of Sonic hedgehog (Shh)-expressing and Shh-responsive (Nkx2-1+ and Gli1+) neurons in the medial amygdala. Specifically, we found that Shh- and Nkx2-1-lineage cells contribute differentially to the dorsal and ventral subdivisions of the postnatal medial amygdala. These Shh- and Nkx2-1-lineage neurons express overlapping and non-overlapping inhibitory neuronal markers, such as Calbindin, FoxP2, nNOS and Somatostatin, revealing diverse fate contributions in discrete medial amygdala nuclear subdivisions. Electrophysiological analysis of the Shh-derived neurons additionally reveals an important functional diversity within this lineage in the medial amygdala. Moreover, inducible Gli1CreER(T2) temporal fate mapping shows that early-generated progenitors that respond to Shh signaling also contribute to medial amygdala neuronal diversity. Lastly, analysis of Nkx2-1 mutant mice demonstrates a genetic requirement for Nkx2-1 in inhibitory neuronal specification in the medial amygdala distinct from the requirement for Nkx2-1 in cerebral cortical development.ConclusionsTaken together, these data reveal a differential contribution of Shh-expressing and Shh-responding cells to medial amygdala neuronal diversity as well as the function of Nkx2-1 in the development of this important limbic system structure.
In the embryonic telencephalon, the pallial-subpallial boundary (PSB) separates the dorsal Pax6+ pallium from the ventral Gsh2+ subpallium. Previous studies have revealed that this region is a source of cells that will populate both the olfactory bulb and basal telencephalic limbic system. However, the level of progenitor cell heterogeneity and developmental genetic regulation of this progenitor region remains to be fully elucidated. In this study we carried out a comprehensive analysis of gene expression patterns at the PSB, in addition to an examination of the combinatorial function of Pax6 and Gsh2 in the specification of the PSB. First, we reveal that the PSB is comprised of a complex mix of molecularly distinct progenitor pools. In addition, by analysis of single Sey, Gsh2, and Sey/Gsh2 double mutant mice, we demonstrate that both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification. Our analysis also reveals that the establishment of the epidermal growth factor receptor positive lateral cortical stream migratory route to the basal telencephalon is Pax6 dependent. Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning.
mortality. The purpose of this paper is to review the biomechanical aspects, clinical features, radiologic criteria, and treatment strategies of AOD. Given that the diagnosis of AOD can be very challenging, a high degree of clinical suspicion is essential to ensure timely recognition and treatment, thus preventing neurological decline or death. Core tip: Atlanto-occipital dislocation (AOD) is being increasingly recognized as a potentially survivable injury as a result of improved prehospital management, increased awareness, and more aggressive management. However, despite overall improved outcomes, AOD is still associated with significant morbidity and mortality. Given that the diagnosis can be very challenging, a high degree of clinical suspicion is essential to ensure timely recognition and treatment, thus preventing neurological decline or death.Hall GC, Kinsman MJ, Nazar RG, Hruska RT, Mansfield KJ, Boakye M, Rahme R. Atlanto-occipital dislocation. INTRODUCTIONIn a recent study of 300 patients with cervical spine trauma, 30% of injuries were located between the occiput and C2. Among these, acute spondylolysis of C2 (hangman's fracture), C1 ring fractures, odontoid fractures, and atlanto-occipital dislocation (AOD) were the most common [1] . Graham AbstractAtlanto-occipital dislocation (AOD) is being increasingly recognized as a potentially survivable injury as a result of improved prehospital management of polytrauma patients and increased awareness of this entity, leading to earlier diagnosis and more aggressive treatment. However, despite overall improved outcomes, AOD is still associated with significant morbidity and MINIREVIEWS 236March 18, 2015|Volume 6|Issue 2|
Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways.
Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments=daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways.
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