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In JoVE (1)
Other Publications (4)
Articles by Carlos A. Lafourcade in JoVE
Neonatal Subventricular Zone Electroporation
David M. Feliciano1, Carlos A. Lafourcade1, Angélique Bordey1
1Department of Neurosurgery and Cellular & Molecular Physiology, Yale University School of Medicine
We demonstrate a minimally invasive technique referred to as neonatal subventricular zone electroporation. The technique consists of injecting plasmid DNA into the lateral ventricles of neonatal pups and applying electrical current to deliver and genetically manipulate neural stem cells
Other articles by Carlos A. Lafourcade on PubMed
Distinctions Among GABAA and GABAB Responses Revealed by Calcium Channel Antagonists, Cannabinoids, Opioids, and Synaptic Plasticity in Rat Hippocampus
Psychopharmacology. Jul, 2008 | Pubmed ID: 18097653
Hippocampal interneurons release gamma-aminobutyric acid (GABA) and produce fast GABA(A)- and slow GABA(B)-inhibitory postsynaptic potentials (IPSPs). The regulation of GABA(B) eIPSPs or the interneurons that produce them are not well understood. In addition, while both micro-opioid receptors (microORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.
Journal of Neurophysiology. Oct, 2009 | Pubmed ID: 19553483
Endogenous cannabinoids (eCBs) mobilized from postsynaptic cells activate presynaptic cannabinoid receptors and thereby inhibit synaptic transmitter release. The inhibition can be either brief (seconds) or long-lasting (minutes to hours). Recent studies provide insight into the presynaptic mechanisms responsible for long-lasting, eCB-mediated long-term depression. Among these, the proteins PKA and RIM1alpha appear to be crucial, although other possibilities are emerging.
Novel MGluR- and CB1R-independent Suppression of GABA Release Caused by a Contaminant of the Group I Metabotropic Glutamate Receptor Agonist, DHPG
PloS One. 2009 | Pubmed ID: 19568435
Metabotropic glutamate receptors (mGluRs) are ubiquitous throughout the body, especially in brain, where they mediate numerous effects. MGluRs are classified into groups of which group I, comprising mGluRs 1 and 5, is especially important in neuronal communication. Group I actions are often investigated with the selective agonist, S-3,5-dihydroxyphenylglycine (DHPG). Despite the selectivity of DHPG, its use has often led to contradictory findings. We now report that a particular commercial preparation of DHPG can produce mGluR-independent effects. These findings may help reconcile some discrepant reports.
Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Feb, 2013 | Pubmed ID: 23392671
Mammalian target of rapamycin (mTOR) hyperactivity in perinatal neural progenitor cells (NPCs) of tuberous sclerosis complex 1 (Tsc1) heterozygote mice leads to heterotopia and abnormal neuronal morphogenesis as seen in patients with tuberous sclerosis. Considering that pathological hyperactive mTOR also occurs in individuals carrying no genetic mutations, we examined whether increasing mTOR activity in neonatal NPCs of wild-type mice would recapitulate the above phenotypes. Electroporation of a plasmid encoding constitutively active Ras-homolog enriched in brain (Rheb(CA)) into subventricular zone NPCs increased mTOR activity in newborn cells. At 19 d post-electroporation (dpe), heterotopia and ectopic cells with a neuronal morphology were observed along the migratory path [rostral migratory stream (RMS)] and in the olfactory bulb (OB). These ectopic cells displayed action potentials and received synaptic inputs identifying them as synaptically integrated neurons. RMS heterotopias contained astrocytes, neurons, and entrapped neuroblasts. Immunostaining at 3 dpe revealed the presence of Mash1(+) Olig2(-) cells in the migratory route accompanied by ectopic neuronal differentiation and altered direction and speed of neuroblast migration at 7 dpe, suggesting a non-cell-autonomous disruption of migration. At >19 dpe, newborn Rheb(CA)-expressing neurons displayed altered distribution and formed micronodules in the OB. In addition, they displayed increased dendritic complexity along with altered membrane biophysics and increased frequency of GABAergic synaptic inputs. OB heterotopia, micronodules, and dendrite hypertrophy were notably prevented by rapamycin treatment, suggesting their mTOR dependence. Collectively, these data show that increasing mTOR activity in neonatal NPCs of wild-type mice recapitulate the pathologies observed in Tsc1 mutant mice. In addition, increased mTOR activity in individuals without known mutations could significantly impact neurogenesis and circuit formation.