Biology subjects

Carames, J. M.

Publications and source records attributed to Carames, J. M..

3 recordsLinked to original sources

bioRxiv2025

A sensitivity-consistency trade-off in memory formation regulated by dentate gyrus inhibition

A core computational challenge for memory systems is the need to balance two opposing demands: (1) sensitivity to subtle input differences for flexible encoding, and (2) consistency to preserve stable, interference-resistant representations. How the brain dynamically regulates this trade-off remains unclear. Here, we show that modulating parvalbumin-expressing (PV+) interneurons in the dentate gyrus regulates this balance by shifting hippocampal computation between sensitivity and consistency regimes. Combining cell-type-specific pharmacogenetics, behavioral assays, and computational modeling, we found that reducing PV+-mediated inhibition during encoding enhanced the subsequent discrimination of similar inputs but it increased vulnerability to interference. In contrast, increased inhibition stabilized memory representations at the cost of discriminability. Together, the results establish PV+ interneurons as key modulators of hippocampal memory processing, enabling the system to prioritize either flexible updating or robust retention based on inhibitory tone at the time of encoding. This sensitivity-consistency continuum may reflect a fundamental organizing principle of memory computation.

neuroscience↗

bioRxiv2020

Hippocampal dentate gyrus coordinates brain-wide communication and memory updating through an inhibitory gating

Distinct forms of memory processing are often causally identified with specific brain regions, but a key facet of memory processing includes linking separated neuronal populations. Using cell-specific manipulations of inhibitory neuronal activity, we discovered a key role of the dentate gyrus (DG) in coordinating dispersed neuronal populations during memory formation. In whole-brain fMRI and electrophysiological experiments, we found that parvalbumin (PV) interneurons in the DG control the functional coupling of the hippocampus within a wider network of neocortical and subcortical structures including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). In a novel object-location task, regulation of PV interneuron activity enhanced or prevented memory encoding and, without effect upon the total number of task activated c-Fos+ cells, revealed a correlation between activated neuronal populations in the hippocampus-PFC-NAc network. These data suggest a critical regulatory role of PV interneurons in the dentate gyrus in brain-wide polysynaptic communication channels and the association of cell assemblies across multiple brain regions.

neuroscience↗

bioRxiv2019

Neuronal identity is maintained in the adult brain through KAT3-dependent enhancer acetylation

Very little is known about the mechanisms responsible for maintaining cell identity in mature tissues. The paralogous type 3 lysine acetyltransferases (KAT3) CBP and p300 are both essential during development, but their specific functions in nondividing differentiated cells remains unclear. Here, we show that when both proteins are simultaneously knocked-out in excitatory neurons of the adult brain, the mice express a rapidly progressing neurological phenotype associated with reduced dendritic complexity and electrical activity, the transcriptional shutdown of neuronal genes, and a dramatic loss of H3K27 acetylation and pro-neural transcription factor binding at neuronal enhancers. The neurons lacking both KAT3 rapidly acquire a molecularly undefined fate with no sign of dedifferentiation, transdifferentiation or death. Restoring CBP expression or lysine acetylation reestablished neuronal-specific transcription. Our experiments demonstrate that KAT3 proteins act as fate-keepers in excitatory neurons and other cell types by jointly safeguarding chromatin acetylation levels at cell type-specific enhancers throughout life.

cell biology↗