Biology subjects

Freitag, F.

Publications and source records attributed to Freitag, F..

4 recordsLinked to original sources

bioRxiv2026

Behavioural Context Shapes Sensory Responses in Vibrissal Motor Cortex

Understanding how motor cortical circuits flexibly transform sensory and contextual information into behavior remains a central challenge. Whether neurons in primary vibrissal motor cortex (M1) multiplex across behaviors or are selectively engaged in context-specific actions is still unclear. To address this question, we trained mice on multiple vibrissal sensorimotor tasks, including a cue-triggered whisking-to-touch task and an air-puff-triggered licking task. Fast-spiking and regular-spiking neurons in layers 2/3 and 5 in vM1 responded robustly within [~]15 ms to air-puff stimulation. In contrast, these same neurons were only weakly modulated during goal-directed whisking-to-touch behavior. Unexpected air-puffs evoked responses in fewer neurons than expected stimuli. Trials in which stimulation elicited whisker movements produced smaller neural responses than trials without whisking. Stimulus-evoked activity in M1 was organized along a spectrum of response profiles with neurons exhibiting varying responses dynamics that cut across laminar and physiological distinctions. This organization of responses is consistent with context-dependent recruitment of M1 neurons. Together, these findings indicate that M1 activity is more closely associated with the selection of specific behavioral responses than with generalized sensory-motor encoding. SignificanceHow motor cortex links sensory input to behavior remains a central question in neuroscience. Do neurons that respond to vibrissal stimuli also participate in whisker-based behaviors, or do they reflect distinct functional states? Here, we show that activity in vM1 is context dependent. Across multiple behaviors, sensory inputs recruit different neuronal populations depending on behavioral context: air-puff stimuli evoke rapid and robust responses, whereas the same neurons are only weakly engaged during goal-directed whisking-to-touch. In addition, expected and unexpected stimuli activate partially distinct ensembles, and sensory responses are attenuated when stimuli directly trigger movement. These findings indicate that M1 does not uniformly encode sensory input; instead, activity reflects context-dependent action selection where neuronal populations are engaged according to behavioral demands.

neuroscience↗

bioRxiv2024

Microbial metabolite-guided CAR T cell engineering enhances anti-tumor immunity via epigenetic-metabolic crosstalk

The microbiome is a complex host factor and key determinant of the outcome of antibody-based and cellular immunotherapy. Its postbiotics are a blend of soluble commensal byproducts that are released into the host environment and have been associated with the regulation of immune homeostasis, particularly through impacts on epigenetics and cell signaling. In this study, we show that the postbiotic pentanoate is metabolized to citrate within the TCA cycle via both the acetyl- and succinyl-CoA entry points, a feature uniquely enabled by the chemical structure of the C5 aliphatic chain. We identified ATP-citrate lyase as the crucial factor that redirects pentanoate-derived citrate from the succinyl-CoA route to the nucleus, thereby linking metabolic output and histone acetylation. This epigenetic-metabolic crosstalk mitigated T cell exhaustion and promoted naive-like differentiation in pentanoate-programmed chimeric antigen receptor (CAR) T cells. The predictive and therapeutic potential of pentanoate was corroborated in two independent patient cohorts and three syngeneic models of CAR T adoptive therapy. Our data demonstrate that postbiotics are integrated into mitochondrial metabolism and subsequently incorporated as epigenetic imprints. This bridge between microbial and mammalian interspecies communication can ultimately impact T cell differentiation and efficacy.

immunology↗

bioRxiv2023

Individuality across environmental context in Drosophila melanogaster

Over the past decade, several studies have demonstrated that idiosyncratic animal behaviors remain consistent over long time periods. The consistency of individually variable behaviors over time is often referred to as an animals individuality, or if consisting of multiple traits personality. However, most experimental studies have focused on individuality in a single, well-defined environmental context, whereas it is well-established from population studies that animal behavior is highly context-dependent. The person-situation debate in humans and decades of observations of animal individuality under intrinsically variable natural conditions raise the question of whether and to what extent animal behavior remains consistent across different situations, such as changing environmental contexts. For instance, one individual might be generally more visually guided than another, or rely only on one particular visual cue, or even on this very cue only in a specific environmental context. Here, we use a combination of both well-established and novel behavioral assays to demonstrate the relationship between individual behavior and variable environmental context under tightly controlled laboratory conditions in the model system Drosophila melanogaster. The consistency of three individual traits (termed exploration, attention, and anxiety) was investigated under changing environmental contexts (temperature, visual cues, arena shape), in both walking and flying flies. We find that individuality is highly context-dependent, but even under the most extreme environmental alterations tested, consistency of behavioral individuality always persisted in at least one of the traits. Furthermore, our quantification reveals a hierarchical order of environmental features influencing individuality. We confirmed this hierarchy using a generalized linear model and a hierarchical linear mixed model. In summary, our work demonstrates that, similar to humans, fly individuality persists across different contexts (albeit worse than across time), and individual differences shape behavior across variable environments. The presence of consistency across situations in flies makes the underlying developmental and functional mechanisms amenable to genetic dissection.

animal behavior and cognition↗

bioRxiv2022

On the functional role of gamma synchronization in the retinogeniculate system of the cat

AO_SCPLOWBSTRACTC_SCPLOWFast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies carried out under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multi-electrode recordings of spiking activity in the retina and the LGN of the cat, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were non-oscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent upon halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.

neuroscience↗