Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition.

The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored.

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.

A cortico-hippocampal learning rule shapes inhibitory microcircuit activity to enhance hippocampal information flow.

How does coordinated activity between distinct brain regions implement a set of learning rules to sculpt information processing in a given neural circuit? Using interneuron cell-type-specific optical activation and pharmacogenetic silencing in vitro, we show that temporally precise pairing of direct entorhinal perforant path (PP) and hippocampal Schaffer collateral (SC) inputs to CA1 pyramidal cells selectively suppresses SC-associated perisomatic inhibition from cholecystokinin (CCK)-expressing interneurons. The CCK interneurons provide a surprisingly strong feedforward inhibitory drive to effectively control the coincident excitation of CA1 pyramidal neurons by convergent inputs. Thus, in-phase cortico-hippocampal activity provides a powerful heterosynaptic learning rule for long-term gating of information flow through the hippocampal excitatory macrocircuit by the silencing of the CCK inhibitory microcircuit.

Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism.

Background: Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the anaphase-promoting complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood.

Results: Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms.

A proteomic screen reveals SCFGrr1 targets that regulate the glycolytic-gluconeogenic switch.

Entry into the cell cycle is regulated by nutrient availability such that cells do not divide when resources are limited. The Skp1-Cul1-F-box (SCF) ubiquitin ligase with the F-box protein Grr1 (SCF(Grr1)) controls the proteolytic turnover of regulators of cell-cycle entry and a glucose sensor, suggesting that it links the cell cycle with nutrient availability. Here, we show that SCF(Grr1) broadly regulates cellular metabolism.

DNA breaks promote genomic instability by impeding proper chromosome segregation.

Background: Unrepaired DNA double-stranded breaks (DSBs) can result in the whole or partial loss of chromosomes. Previously, we showed that the ends of broken chromosomes remain associated. Here, we have examined the machinery that holds broken chromosome ends together, and we have explored the behavior of broken chromosomes as they pass through mitosis.