Correlated Somatosensory Input in Parvalbumin/Pyramidal Cells in Mouse Motor Cortex.

In mammalian cortex, feedforward excitatory connections recruit feedforward inhibition. This is often carried by parvalbumin (PV+) interneurons, which may densely connect to local pyramidal (Pyr) neurons. Whether this inhibition affects all local excitatory cells indiscriminately or is targeted to specific subnetworks is unknown.

PCSK9 deficiency alters brain lipid composition without affecting brain development and function.

PCSK9 induces lysosomal degradation of the low-density lipoprotein (LDL) receptor (LDLR) in the liver, hereby preventing removal of LDL cholesterol from the circulation. Accordingly, PCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia. In addition, PCSK9 inactivation alters the levels of several other circulating lipid classes and species.

Organization of Cortical and Thalamic Input to Inhibitory Neurons in Mouse Motor Cortex.

Intracortical inhibition in motor cortex (M1) regulates movement and motor learning. If cortical and thalamic inputs target different inhibitory cell types in different layers, then these afferents may play different roles in regulating M1 output. Using mice of both sexes, we quantified input to two main classes of M1 interneurons, parvalbumin+ (PV+) cells and somatostatin+ (SOM+) cells, using monosynaptic rabies tracing.

BRAFV600E expression in neural progenitors results in a hyperexcitable phenotype in neocortical pyramidal neurons.

Somatic mutations have emerged as the likely cause of focal epilepsies associated with developmental malformations and epilepsy-associated glioneuronal tumors (GNT). Somatic BRAFV600E mutations in particular have been detected in the majority of low-grade neuroepithelial tumors (LNETS) and in neurons in focal cortical dysplasias adjacent to epilepsy-associated tumors. Furthermore, conditional expression of an activating BRAF mutation in neocortex causes seizures in mice.

In vivo transgenic expression of collybistin in neurons of the rat cerebral cortex.

Collybistin (CB) is a guanine nucleotide exchange factor selectively localized to γ-aminobutyric acid (GABA)ergic and glycinergic postsynapses. Active CB interacts with gephyrin, inducing the submembranous clustering and the postsynaptic accumulation of gephyrin, which is a scaffold protein that recruits GABA receptors (GABA Rs) at the postsynapse. CB is expressed with or without a src homology 3 (SH3) domain.

Partial Breakdown of Input Specificity of STDP at Individual Synapses Promotes New Learning.

Unlabelled: Hebbian-type learning rules, which underlie learning and refinement of neuronal connectivity, postulate input specificity of synaptic changes. However, theoretical analyses have long appreciated that additional mechanisms, not restricted to activated synapses, are needed to counteract positive feedback imposed by Hebbian-type rules on synaptic weight changes and to achieve stable operation of learning systems. The biological basis of such mechanisms has remained elusive.

Advantages and limitations of the use of optogenetic approach in studying fast-scale spike encoding.

Understanding single-neuron computations and encoding performed by spike-generation mechanisms of cortical neurons is one of the central challenges for cell electrophysiology and computational neuroscience. An established paradigm to study spike encoding in controlled conditions in vitro uses intracellular injection of a mixture of signals with fluctuating currents that mimic in vivo-like background activity. However this technique has two serious limitations: it uses current injection, while synaptic activation leads to changes of conductance, and current injection is technically most feasible in the soma, while the vast majority of synaptic inputs are located on the dendrites.

Exposure of developing chicks to perfluorooctanoic acid induces defects in prehatch and early posthatch development.

There is increasing concern over the widespread use of perfluorinated chemicals, which accumulate in various tissues and penetrate the mammalian fetus. A chick model was established for the rapid evaluation of teratogenicity of these chemicals, an important issue because developmental defects often occur at lower exposures than those required for adult systemic toxicity. Chicken eggs were injected with varying doses of perfluorooctanoic acid prior to incubation.