Sunday, January 5th, 2025

Time	Event
8:31a	Single-nucleus transcriptomics reveals time-dependent and cell-type-specific effects of psilocybin on gene expression There is growing interest to investigate classic psychedelics as potential therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin leads to persisting neural and behavioral changes. The durability of psilocybin's effects suggests that there are likely alterations of gene expression at the transcriptional level. In this study, we performed single-nucleus RNA sequencing of the dorsal medial frontal cortex of male and female mice. Samples were collected at 1, 2, 4, 24, or 72 hours after psilocybin or ketamine administration and from control animals. At baseline, major excitatory and GABAergic cell types selectively express particular serotonin receptor transcripts. The psilocybin-evoked differentially expressed genes in excitatory neurons were involved in synaptic plasticity, which were distinct from genes enriched in GABAergic neurons that contribute to mitochondrial function and cellular metabolism. The effect of psilocybin on gene expression was time-dependent, including an early phase at 1-2 hours followed by a late phase at 72 hours of transcriptional response after administration. Ketamine administration produced transcriptional changes that show a high degree of correlation to those induced by psilocybin. Collectively, the results reveal that psilocybin produces time-dependent and cell-type specific changes in gene expression in the medial frontal cortex, which may underpin the drug's long-term effects on neural circuits and behavior. (Comment on this)
10:30p	Misspelled-word reading modulates late cortical dynamics Literate humans can effortlessly interpret tens of thousands of words, even when the words are sometimes written incorrectly. This phenomenon suggests a flexible nature of reading that can endure a certain amount of noise. In this study, we investigated where and when brain responses diverged for conditions where misspelled words were resolved as real words or not. We used magnetoencephalography (MEG) to track the cortical activity as the participants read words with different degrees of misspelling that were perceived to range from real words to complete pseudowords, as confirmed by their behavioral responses. In particular, we were interested in how lexical information survives (or not) along the uncertainty spectrum, and how the corresponding brain activation patterns evolve spatiotemporally. We identified three brain regions that were notably modulated by misspellings: left ventral occipitotemporal cortex (vOT), superior temporal cortex (ST), and precentral cortex (pC). This suggests that resolving misspelled words into stored concepts involves an interplay between orthographic, semantic, and phonological processing. Temporally, these regions showed fairly late and sustained responses selectively to misspelled words. Specifically, an increasing level of misspelling increased the response in ST from 300 ms after stimulus onset; a functionally fairly similar but weaker effect was observed in pC. In vOT, misspelled words were sharply distinguished from real words notably later, after 700 ms. A linear mixed effects (LME) analysis further showed that pronounced and long-lasting misspelling effects appeared first in ST and then in pC, with shorter-lasting activation also observed in vOT. We conclude that reading misspelled words engages brain areas typically associated with language processing, but in a manner that cannot be interpreted merely as a rapid feedforward mechanism. Instead, feedback interactions likely contribute to the late effects observed during misspelled-word reading. (Comment on this)
10:30p	Representational drift reflects ongoing balancing of stochastic changes by Hebbian learning Recent evidence indicates that even under stable environmental and behavioural conditions responses to sensory stimuli undergo continuous reformatting over the course of days, a condition described as representational drift. However, the processes underlying this phenomenon remain poorly understood. Examining the dynamics of signal and noise correlations among neuron pairs in chronic calcium imaging experiments in the mouse auditory cortex, we investigate how activity-dependent, Hebbian-like plasticity, and activity-independent, stochastic synaptic processes contribute to representational drift. We found that signal correlations predict future noise correlations, suggesting that stimulus-induced co-activation leads to increased effective connectivity between neuron pairs. Moreover, simple linear network models were able to account for the observed temporal dependencies between signal and noise correlations, but only if both Hebbian-like plasticity and stochastic changes of either inputs or recurrent synapses contribute to representational drift. In conclusion, our findings suggest that continuous sensory input-driven Hebbian-like plasticity can balance ongoing stochastic synaptic changes, thereby preventing the network's functional degradation. (Comment on this)
11:45p	C. elegans interprets dietary quality through context-dependent serotonergic modulation Animals sense their metabolic needs to guide foraging decisions using neuronal pathways that are only partly understood. Here, we systematically investigate how foraging in the nematode Caenorhabditis elegans is influenced by its bacterial diet, E. coli. By screening C. elegans behavior on 3983 E. coli knockout strains, we identified 22 E. coli metabolic mutants that are aversive to C. elegans in a long-term foraging assay. These include the global metabolic regulator CRP and genes affecting cysteine synthesis, vitamin B6 synthesis, and iron uptake. Serotonin, a neurotransmitter associated with feeding in many animals, allows C. elegans to distinguish wild-type E. coli from these mediocre diets through bidirectional signaling. Serotonin produced by the ADF serotonergic neurons supports attraction to wild-type E. coli with the serotonin receptor genes ser-4 and ser-5, whereas serotonin produced by the NSM serotonergic neurons differentially drives aversion to two mediocre diets through four serotonin receptor genes, ser-1, ser-7, mod-1, and lgc-50. Serotonin receptors act in multiple target neurons, including octopamine-producing neurons that suppress aversion across all diets. In addition, dopamine promotes aversion, in part by inhibiting octopaminergic neurons. These results reveal interactions between neuromodulatory circuits in the context-dependent evaluation of dietary quality. (Comment on this)

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