Biology subjects

Chatzi, C.

Publications and source records attributed to Chatzi, C..

3 recordsLinked to original sources

bioRxiv2026

Biased synaptic activation of dentate granule cells by exercise reflects inputs from the lateral entorhinal cortex.

Hippocampal dentate granule cells receive multisensory information from the entorhinal cortex in a laminated and functionally segregated manner. We previously reported that brief periods of voluntary exercise in mice increased EPSCs and dendritic spines for inputs from the lateral, but not the medial, entorhinal cortex. Here we asked whether laminar specificity was due to molecular changes specific to distal granule cell dendrites or rather was dependent on upstream drive from the entorhinal cortex. Selective chemogenetic stimulation of either lateral entorhinal cortex (LEC) or the medial entorhinal cortex (MEC) increased granule cell dendritic spine density in the selected pathway. However, the preponderance of exercise-activated cells originated from LEC based on expression of an activity-dependent retrograde virus in Fos-TRAP mice. Our results indicate that the preferential activation by exercise reflects the drive of locomotor-related inputs from the lateral entorhinal cortex rather than selective molecular mechanisms in distal dendrites of dentate granule cells. How this activation pattern affects other salient stimuli involving contextual or spatial cues may underlie the benefits of exercise on learning and memory.

neuroscience↗

bioRxiv2019

Exercise-induced enhancement of synaptic functiontriggered by the inverse BAR protein, Mtss1L.

Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked mature hippocampal dentate granule cells that were specifically activated during exercise using conditional Fos-TRAP mice. Only a few dentate granule cells were active at baseline, but two hours of voluntary exercise markedly increased the number of activated neurons. Activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied gene in the adult brain. Overexpression of Mtss1L in neurons increased spine density, leading us to hypothesize that its I-BAR domain initiated membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses. One Sentence SummarySingle episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.

neuroscience↗

bioRxiv2017

Preferential targeting of lateral entorhinal inputs onto newly integrated granule cells

Mature dentate granule cells in the hippocampus receive input from the entorhinal cortex via the perforant path in precisely arranged lamina, with medial entorhinal axons innervating the middle molecular layer and lateral entorhinal cortex axons innervating the outer molecular layer. Although vastly outnumbered by mature granule cells, adult-generated newborn granule cells play a unique role in hippocampal function, which has largely been attributed to their enhanced excitability and plasticity (Schmidt-Hieber et al., 2004; Ge et al., 2007). Inputs from the medial and lateral entorhinal cortex carry different informational content, thus the distribution of inputs onto newly integrated granules will affect their function in the circuit. Therefore we examined the functional innervation and synaptic maturation of newly-generated dentate granule cells using retroviral labeling in combination with selective optogenetic activation of medial or lateral entorhinal inputs. Our results indicate that lateral entorhinal inputs provide nearly all the functional innervation of newly integrated granule cells. Despite preferential functional targeting, the dendritic spine density of immature granule cells was not increased in the outer molecular layer compared to the middle molecular layer. However, chronic blockade of neurotransmitter release in medial entorhinal axons with tetanus toxin disrupted normal synapse development from both medial and lateral entorhinal inputs. Our results support a role for preferential lateral perforant path input onto newly generated neurons in mediating pattern separation, but also indicates that medial perforant path input is necessary for normal synaptic development.\n\nSignificance StatementThe formation of episodic memories involves the integration of contextual and spatial information. Newly integrated neurons in the dentate gyrus of the hippocampus play a critical role in this process, despite constituting only a minor fraction of total granule cells. Here we demonstrate that these neurons preferentially receive information thought to convey the context of an experience - a unique role that each newly integrated granule cell serves for about a month before reaching maturity.

neuroscience↗