Biology subjects

Bengtson, C. P.

Publications and source records attributed to Bengtson, C. P..

3 recordsLinked to original sources

bioRxiv2024

Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing

Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabies viruses to investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain engaging in widespread functional communication, with acetylcholinergic neurons driving glioblastoma invasion. We uncovered patient-specific and tumor cell state-dependent differences in synaptogenic gene expression associated with neuron-tumor connectivity and subsequent invasivity. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous neuronal activity inhibition and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a viral strategy to tackle glioblastoma. Together, this study provides a framework to comprehensively characterize neuron-tumor networks and target glioblastoma.

cancer biology↗

bioRxiv2024

Hippocampal DNA methylation promotes memory persistence by facilitating systems consolidation and cortical engram stabilisation.

The long-term stabilization of memory traces or engram involves the rapid formation of cortical engrams during encoding that mature functionally over time guided by the activity of the hippocampus. The molecular mechanisms that regulate this process remain largely unknown. Here, we found that hippocampal DNA methylation converts short-lasting into long-lasting memories by promoting systems consolidation and the stabilization of cortical engrams.

neuroscience↗

bioRxiv2023

Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice

Long-term memories are believed to be encoded by unique transcriptional signatures in the brain. The expression of immediate early genes (IEG) promotes structural and molecular changes required for memory consolidation. Recent evidence has shown that the brain is equipped with mechanisms that not only promote, but actively constrict memory formation. However, it remains unknown whether IEG expression may play a role in memory suppression. Here we uncovered a novel function of the IEG neuronal PAS domain protein 4 (Npas4), as an inducible memory suppressor gene of highly salient aversive experiences. Using a contextual fear conditioning paradigm, we found that low stimulus salience leads to monophasic Npas4 expression, while highly salient learning induces a biphasic expression of Npas4 in the hippocampus. The later phase requires NMDA receptor activity and is independent of dopaminergic neurotransmission. Our in vivo pharmacological and genetic manipulation experiments suggested that the later phase of Npas4 expression restricts the consolidation of a fear memory and promote behavioral flexibility, by facilitating fear extinction and the contextual specificity of fear responses. Moreover, immunofluorescence and electrophysiological analysis revealed a concomitant increase in synaptic input from cholecystokinin (CCK)-expressing interneurons. Our results demonstrate how salient experiences evoke unique temporal patterns of IEG expression that fine-tune memory consolidation. Moreover, our study provides evidence for inducible gene expression associated with memory suppression as a possible mechanism to balance the consolidation of highly salient memories, and thereby to evade the formation of maladaptive behavior.

neuroscience↗