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Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex
P.P. Kale, V. Addepalli / Int. J. Devl Neuroscience 30 (2012) 640–671
Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex S. Lodato a,∗ , C. Rouaux a , K.B. Quast b , C. Jantrachotechatchawan a , T.K. Hensch b , P. Arlotta a a
Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA b Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, USA
E-mail address: [email protected] (S. Lodato). The activity and function of the mammalian cerebral cortex rely on the integration of an extraordinary diversity of excitatory projection neurons and inhibitory interneurons into balanced local circuitry. The developmental events governing the proper interaction between excitatory projection neurons and inhibitory interneurons are poorly understood. Here, we report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons into cortical layers. We find that in Fezf2−/− cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons. This results in physiological imbalance of excitation due to altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birth date, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry. doi:10.1016/j.ijdevneu.2012.03.290
Stereological estimation of volume, total neuron number and neuronal nuclear area of chick brainstem auditory nuclei and hippocampus following prenatal patterned and unpatterned sound stimulation Tania Sanyal (Chatterjee) ∗ , T.C. Nag, Shashi Wadhwa All India Institute of Medical Sciences, India Prenatal auditory stimulation in chicks with species specific sound and music of moderate sound pressure level (65 dB) facilitates spatial orientation and learning associated with morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. To explore whether prenatal patterned (music) and unpatterned (noise) sound of high sound pressure level (110 dB) has any effect on the morphology of these regions, we have measured the total neuron and glia number, mean neuronal nuclear area and the total volume of brainstem auditory nuclei and hippocampus of post hatch day 1 (PH1) chicks, by using the stereology software. Both hippocampus and brainstem auditory nuclei showed a significant increase in total volume (p ≤ 0.001), total neuron number (p ≤ 0.001) and mean neuronal nuclear area (p ≤ 0.001) in music stimulated group as compared to control. In contrast, noise treated group showed significantly reduced volume (p ≤ 0.001), total neuron number (p ≤ 0.001) and mean neuronal nuclear area (hippocampus: p ≤ 0.002, brainstem: p ≤ 0.001) in both the regions. Percentage of neurons with large nuclear area was more in the music stimulated group and less in the noise stimulated group as compared to control. Glial cell number was significantly increased (p ≤ 0.001) in both the experimental groups being highest in the noise stimulated group. Neuron to glia ratio in hippocampus remained unaltered between control and music, but was higher in
659
the noise stimulated group. In brainstem auditory nuclei, this ratio was increased in both the experimental groups compared to control. It is thus evident that though the sound pressure level in both experimental groups is the same at 110 dB, the differential change in the morphological parameters indicates that the characteristics of the sound are important in mediating the effects. doi:10.1016/j.ijdevneu.2012.03.291
Effect of bone marrow stromal cells transplantation on sensorimotor and autonomic function in complete spinal cord transection injury rats Suneel Kumar 1,∗ , Suman Jain 1 , Sujata Mohanty 2 , Jitendra Behari 3 , Ajay Pal 1 , Krishan Gopal 2 , Rashmi Mathur 1 1
Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110026, India 2 Department of Stem Cell Facility, All India Institute of Medical Sciences (AIIMS), New Delhi 110026, India 3 School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110016, India
Introduction: Spinal cord injury (SCI) leads to a devastating cascade of events including anatomical, physiological and neurochemical changes often leading to neuronal cell death. Loss of motor and altered sensory function; development of chronic or neuropathic pain may develop depending on injury location and severity. Both human and rodent bone marrow stromal cells (BMSC) have been studied and demonstrated behavioral efficacy (BBB score) in many rodent SCI. We report the effect of BMSC transplantation on sensorimotor and autonomic function in complete spinal cord transection (CT-SCI, T13) injury rats. Methods: Adult male Wistar rats were divided into Sham, SCI + Vehicle and SCI + BMSC groups. In ketamine and xylazine (60 and 10 mg/kg BW) anesthetized rats, laminectomy followed by complete spinal cord transection (T13) was done. BBB score, tail flick latencies (TFL) to various temperatures; hot plate latency (HPL); threshold of tail flick (TTF); acetone test (AT) and bladder control were assessed during 8 weeks. Rat BMSCs were cultured and identified the presence of specific cell-surface antigens (CD44, CD90, CD45 and HLAII) using flowcytometry. PKH26 labelled BMSCs (∼2.5 × 105 cells) were transplanted post-SCI day 9 at the site of injury and rats were sacrificed at wk 8. Results: BMSCs were non-hematopoietic and in undifferentiated state. There was a significant recovery in sensorimotor parameters (post-SCI wk 2–8 in BBB score; wk 6–8 in TFL, HPL, TTF and AT) by BMSC transplantation. Bladder recovery was significantly faster (p < 0.02) and lesion volume was reduced in SCI + BMSC group. BMSCs were observed in spinal cord around the injury site and were positive for neuronal, astrocytes and oligodendrocytes markers (III tubulin, GFAP and Olig4, respectively). Discussion: Our results suggest the beneficial effects of BMSC transplantation on sensorimotor and bladder control in CT-SCI rats. The results are supported by the reduction of lesion volume and differentiation of BMSCs in neuronal and glial cells. doi:10.1016/j.ijdevneu.2012.03.293
Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex S. Lodato a,∗ , C. Rouaux a , K.B. Quast b , C. Jantrachotechatchawan a , T.K. Hensch b , P. Arlotta a a
Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA b Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, USA
E-mail address: [email protected] (S. Lodato). The activity and function of the mammalian cerebral cortex rely on the integration of an extraordinary diversity of excitatory projection neurons and inhibitory interneurons into balanced local circuitry. The developmental events governing the proper interaction between excitatory projection neurons and inhibitory interneurons are poorly understood. Here, we report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons into cortical layers. We find that in Fezf2−/− cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons. This results in physiological imbalance of excitation due to altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birth date, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry. doi:10.1016/j.ijdevneu.2012.03.290
Stereological estimation of volume, total neuron number and neuronal nuclear area of chick brainstem auditory nuclei and hippocampus following prenatal patterned and unpatterned sound stimulation Tania Sanyal (Chatterjee) ∗ , T.C. Nag, Shashi Wadhwa All India Institute of Medical Sciences, India Prenatal auditory stimulation in chicks with species specific sound and music of moderate sound pressure level (65 dB) facilitates spatial orientation and learning associated with morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. To explore whether prenatal patterned (music) and unpatterned (noise) sound of high sound pressure level (110 dB) has any effect on the morphology of these regions, we have measured the total neuron and glia number, mean neuronal nuclear area and the total volume of brainstem auditory nuclei and hippocampus of post hatch day 1 (PH1) chicks, by using the stereology software. Both hippocampus and brainstem auditory nuclei showed a significant increase in total volume (p ≤ 0.001), total neuron number (p ≤ 0.001) and mean neuronal nuclear area (p ≤ 0.001) in music stimulated group as compared to control. In contrast, noise treated group showed significantly reduced volume (p ≤ 0.001), total neuron number (p ≤ 0.001) and mean neuronal nuclear area (hippocampus: p ≤ 0.002, brainstem: p ≤ 0.001) in both the regions. Percentage of neurons with large nuclear area was more in the music stimulated group and less in the noise stimulated group as compared to control. Glial cell number was significantly increased (p ≤ 0.001) in both the experimental groups being highest in the noise stimulated group. Neuron to glia ratio in hippocampus remained unaltered between control and music, but was higher in
659
the noise stimulated group. In brainstem auditory nuclei, this ratio was increased in both the experimental groups compared to control. It is thus evident that though the sound pressure level in both experimental groups is the same at 110 dB, the differential change in the morphological parameters indicates that the characteristics of the sound are important in mediating the effects. doi:10.1016/j.ijdevneu.2012.03.291
Effect of bone marrow stromal cells transplantation on sensorimotor and autonomic function in complete spinal cord transection injury rats Suneel Kumar 1,∗ , Suman Jain 1 , Sujata Mohanty 2 , Jitendra Behari 3 , Ajay Pal 1 , Krishan Gopal 2 , Rashmi Mathur 1 1
Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110026, India 2 Department of Stem Cell Facility, All India Institute of Medical Sciences (AIIMS), New Delhi 110026, India 3 School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110016, India
Introduction: Spinal cord injury (SCI) leads to a devastating cascade of events including anatomical, physiological and neurochemical changes often leading to neuronal cell death. Loss of motor and altered sensory function; development of chronic or neuropathic pain may develop depending on injury location and severity. Both human and rodent bone marrow stromal cells (BMSC) have been studied and demonstrated behavioral efficacy (BBB score) in many rodent SCI. We report the effect of BMSC transplantation on sensorimotor and autonomic function in complete spinal cord transection (CT-SCI, T13) injury rats. Methods: Adult male Wistar rats were divided into Sham, SCI + Vehicle and SCI + BMSC groups. In ketamine and xylazine (60 and 10 mg/kg BW) anesthetized rats, laminectomy followed by complete spinal cord transection (T13) was done. BBB score, tail flick latencies (TFL) to various temperatures; hot plate latency (HPL); threshold of tail flick (TTF); acetone test (AT) and bladder control were assessed during 8 weeks. Rat BMSCs were cultured and identified the presence of specific cell-surface antigens (CD44, CD90, CD45 and HLAII) using flowcytometry. PKH26 labelled BMSCs (∼2.5 × 105 cells) were transplanted post-SCI day 9 at the site of injury and rats were sacrificed at wk 8. Results: BMSCs were non-hematopoietic and in undifferentiated state. There was a significant recovery in sensorimotor parameters (post-SCI wk 2–8 in BBB score; wk 6–8 in TFL, HPL, TTF and AT) by BMSC transplantation. Bladder recovery was significantly faster (p < 0.02) and lesion volume was reduced in SCI + BMSC group. BMSCs were observed in spinal cord around the injury site and were positive for neuronal, astrocytes and oligodendrocytes markers (III tubulin, GFAP and Olig4, respectively). Discussion: Our results suggest the beneficial effects of BMSC transplantation on sensorimotor and bladder control in CT-SCI rats. The results are supported by the reduction of lesion volume and differentiation of BMSCs in neuronal and glial cells. doi:10.1016/j.ijdevneu.2012.03.293