Synaptic Vesicle Glycoprotein 2A Knockout in Parvalbumin and Somatostatin Interneurons Drives Seizures in the Postnatal Mouse Brain

Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic protein targeted by the antiseizure drug levetiracetam. One or more of the three SV2 genes is expressed in all neurons and is essential to normal neurotransmission. Loss of SV2A results in a seizure phenotype in mice and mutations in humans are also linked to congenital seizures. How… Continue reading Synaptic Vesicle Glycoprotein 2A Knockout in Parvalbumin and Somatostatin Interneurons Drives Seizures in the Postnatal Mouse Brain

Estrogen-Regulated Lateral Septal Kisspeptin Neurons Abundantly Project to GnRH Neurons and the Hypothalamic Supramammillary Nucleus

While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KPLS) neurons of the lateral septum. As established previously, Kiss1 expression in this region is low and regulated by estrogen receptor- and GABAB receptor-dependent mechanisms. Our present experiments on Kiss1-Cre/ZsGreen knock-in mice revealed that transgene… Continue reading Estrogen-Regulated Lateral Septal Kisspeptin Neurons Abundantly Project to GnRH Neurons and the Hypothalamic Supramammillary Nucleus

Development of Differential Sublaminar Feedforward Inhibitory Circuits in CA1 Hippocampus Requires Satb2

Pyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we… Continue reading Development of Differential Sublaminar Feedforward Inhibitory Circuits in CA1 Hippocampus Requires Satb2

Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry

Extracellular matrix (ECM) is a network of macromolecules which has two forms—perineuronal nets (PNNs) and a diffuse ECM (dECM)—both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how… Continue reading Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry

Disinhibition across Secondary Motor Cortical Regions during Motor Sequence Learning: A TMS-EEG Study

Secondary motor cortical regions, such as the supplementary motor area (SMA), are involved in planning and learning motor sequences; however, the neurophysiological mechanisms across these secondary cortical networks remain poorly understood. In the primary motor cortex, changes in excitatory and inhibitory neurotransmission (E:I balance) accompany motor sequence learning. In particular, there is an early reduction… Continue reading Disinhibition across Secondary Motor Cortical Regions during Motor Sequence Learning: A TMS-EEG Study

Large Donor CRISPR for Whole-Coding Sequence Replacement of Cell Adhesion Molecule LRRTM2

The cell adhesion molecule leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in… Continue reading Large Donor CRISPR for Whole-Coding Sequence Replacement of Cell Adhesion Molecule LRRTM2

Mapping mRNA through its life cycle within a cell

When Xiao Wang applied to faculty jobs, many of the institutions where she interviewed thought her research proposal — to study the life cycle of RNA in cells and how it influences normal development and disease — was too broad. However, that was not the case when she interviewed at MIT, where her future colleagues… Continue reading Mapping mRNA through its life cycle within a cell