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Mahn, M.

Publications and source records attributed to Mahn, M..

5 recordsLinked to original sources

Nethobench: Forecasting design and conditioning shape the structural realism of generated neural dynamics

Forecasting models are increasingly used to model neural population activity, yet existing benchmarks typically evaluate them by pointwise predictive fidelity to held-out observations. In stochastic, partially observed systems, agreement with one sampled realization is distinct from preserving the statistical and dynamical structure of the process. We introduce Nethobench, a benchmark that evaluates structural agreement across five metric families: distributional, temporal--spectral, relational, geometric, and state-dynamical. We validate Nethobench using targeted perturbations and stochastic systems with known dynamics, and apply it to mouse calcium imaging, mouse Neuropixels recordings, and human intracranial recordings, using empirical references to calibrate interpretation. Nethobench detects targeted structural failures and assigns high scores to independent samples from the correct synthetic process despite trajectory mismatch. It tracks structural changes during training and under domain shift. Model comparisons reveal how forecasting formulation, architecture, training regime, and loss shape structural profiles, while OmniMouse input ablations improve all five family means when behavior is added to video in one held-out session. In Brain Treebank, analog retrieval passes more structural checks while a multistep GRU better predicts the observed realization. These results motivate reporting calibrated family-level structural metrics alongside pointwise accuracy, proper probabilistic scores, and task-specific endpoints when evaluating neural forecasts across species and recording modalities.

neuroscience↗

Neural mechanisms of adaptive value coding in the amygdala

To address their needs, animals must optimize behavior by integrating external cues with internal state signals, such as hunger or thirst, environmental conditions, and past experiences. Accordingly, the perceived value of a reward varies depending on an animals current needs. Updating the specific value of rewards predicted by external cues depends on the basolateral amygdala (BLA). However, neurophysiological investigations have centered around the assumption of stimulus-invariant value representations and have not been able to account for behavioral findings that support the BLAs ability to represent stimulus-specific value of distinct appetitive or aversive outcomes. To address how the BLA encodes and updates stimulus-specific value representations, we exposed head-fixed mice to distinct sets of gustatory rewards while tracking perceived value using lick microstructural analysis. Two-photon calcium imaging of BLA principal neurons revealed that the magnitude of the BLA population response scaled with perceived reward value and that the values of different rewards were encoded by distinct neuronal subpopulations. Moreover, reward representations rapidly re-scaled when mice were exposed to a reward that was larger than all previous rewards. Finally, value representations depended on an animals internal state as thirst selectively increased the responses to water rewards whereas aversive experiences strongly attenuated responses to sucrose. Our findings demonstrate that value representations in the BLA are stimulus-specific and highly adaptive to account for changes in relative reward value and to reflect an animals current affective and homeostatic state. This mechanism enables sensory-specific value updates necessary for state-adapted decision making and learning.

neuroscience↗

Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons

The medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity. We show that mPFC neurons that project to the basolateral amygdala display unique spatial patterns of local-circuit synaptic connectivity within the mPFC, which distinguish them from the general mPFC cell population. Moreover, the intrinsic properties of the postsynaptic mPFC cell and anatomical position of both cells jointly account for ~7.5% of the variation in probability of connection between mPFC neurons, with anatomical distance and laminar position explaining most of this fraction in variation. Our findings demonstrate a functional segregation of mPFC excitatory neuron subnetworks, and reveal the factors determining connectivity in the mPFC.

neuroscience↗

Optogenetic silencing of neurotransmitter release with a naturally occurring invertebrate rhodopsin

Information is carried between brain regions through neurotransmitter release from axonal presynaptic terminals. Understanding the functional roles of defined neuronal projection pathways in cognitive and behavioral processes requires temporally precise manipulation of their activity in vivo. However, existing optogenetic tools have low efficacy and off-target effects when applied to presynaptic terminals, while chemogenetic tools are difficult to control in space and time. Here, we show that a targeting-enhanced mosquito homologue of the vertebrate encephalopsin (eOPN3) can effectively suppress synaptic transmission through the Gi/o signaling pathway. Brief illumination of presynaptic terminals expressing eOPN3 triggers a lasting suppression of synaptic output that recovers spontaneously within minutes in vitro as well as in vivo. In freely moving mice, eOPN3-mediated suppression of dopaminergic nigrostriatal afferents leads to an ipsiversive rotational bias. We conclude that eOPN3 can be used to selectively suppress neurotransmitter release at synaptic terminals with high spatiotemporal precision, opening new avenues for functional interrogation of long-range neuronal circuits in vivo.

neuroscience↗

High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

Optogenetic silencing allows time-resolved functional interrogation of defined neuronal populations. However, the limitations of inhibitory optogenetic tools impose stringent constraints on experimental paradigms. The high light power requirement of light-driven ion pumps and their effects on intracellular ion homeostasis pose unique challenges, particularly in experiments that demand inhibition of a widespread neuronal population in vivo. Guillardia theta anion-conducting channelrhodopsins (GtACRs) are promising in this regard, due to their high single-channel conductance and favorable photon-ion stoichiometry. However, GtACRs show poor membrane targeting in mammalian cells, and the activity of such channels can cause transient excitation in the axon due to an excitatory chloride reversal potential in this compartment. Here we address both problems by enhancing membrane targeting and subcellular compartmentalization of GtACRs. The resulting GtACR-based optogenetic tools show improved photocurrents, greatly reduced axonal excitation, high light sensitivity and rapid kinetics, allowing highly efficient inhibition of neuronal activity in the mammalian brain.

neuroscience↗