Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development.

Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11-13, 28-42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features.

Distinct cellular mediators drive the Janus faces of toll-like receptor 4 regulation of network excitability which impacts working memory performance after brain injury.

The mechanisms by which the neurophysiological and inflammatory responses to brain injury contribute to memory impairments are not fully understood. Recently, we reported that the innate immune receptor, toll-like receptor 4 (TLR4) enhances AMPA receptor (AMPAR) currents and excitability in the dentate gyrus after fluid percussion brain injury (FPI) while limiting excitability in controls. Here, we examine the cellular mediators underlying TLR4 regulation of dentate excitability and its impact on memory performance.

Toll-like Receptor 4 Signaling in Neurons Enhances Calcium-Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Currents and Drives Post-Traumatic Epileptogenesis.

Objective: Traumatic brain injury is a major risk factor for acquired epilepsies, and understanding the mechanisms underlying the early pathophysiology could yield viable therapeutic targets. Growing evidence indicates a role for inflammatory signaling in modifying neuronal excitability and promoting epileptogenesis. Here we examined the effect of innate immune receptor Toll-like receptor 4 (TLR4) on excitability of the hippocampal dentate gyrus and epileptogenesis after brain injury.

A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism.

We have investigated delivery of protein therapeutics from the bloodstream into the brain using a mouse model of late-infantile neuronal ceroid lipofuscinosis (LINCL), a lysosomal disease due to deficiencies in tripeptidyl peptidase 1 (TPP1). Supraphysiological levels of TPP1 are delivered to the mouse brain by acute intravenous injection when co-administered with K16ApoE, a peptide that in trans mediates passage across the blood-brain barrier (BBB). Chronic treatment of LINCL mice with TPP1 and K16ApoE extended the lifespan from 126 to >294 days, diminished pathology, and slowed locomotor dysfunction.

Reelin signaling specifies the molecular identity of the pyramidal neuron distal dendritic compartment.

The apical dendrites of many neurons contain proximal and distal compartments that receive synaptic inputs from different brain regions. These compartments also contain distinct complements of ion channels that enable the differential processing of their respective synaptic inputs, making them functionally distinct. At present, the molecular mechanisms that specify dendritic compartments are not well understood.