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Lottem, E.

Publications and source records attributed to Lottem, E..

5 recordsLinked to original sources

Control of Male Mouse Copulatory Behavior by Midbrain Dopamine Neurons

Ejaculation in male mice and humans requires intravaginal thrusting movements following penile intromission, yet the underlying neural mechanisms remain poorly understood. In this study, we used fiber photometry to record real-time activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of male mice during copulation across six sexual interactions, in order to investigate how these dynamics change with experience and to examine their functional significance. Contrary to expectations, phasic VTA DA activity remained stable across sessions, showing time-locked responses to mounts, penile intromission, individual thrusts, and ejaculation, indicating experience-independent neural representations of all copulatory events. Notably, thrusting-related activity sharply declined just before ejaculation. Optogenetic inhibition of DA neurons disrupted thrusting behavior, but did not block ejaculation, suggesting DA signaling is critical for sustaining copulatory actions rather than triggering ejaculation itself. While prevailing theories frame VTA DA activity as primarily experience-dependent or centered on reward prediction, we here highlight its role in behavioral persistence during copulation. More broadly, our findings extend understanding of DA function beyond classical reward paradigms to the regulation of innate complex, goal-directed behaviors.

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Enhanced reward coding and condition-independent dynamics in optogenetically identified corticostriatal neurons in monkeys

The basal ganglia are considered to be the site where cortical sensorimotor and dopaminergic reward information interact to potentiate and select actions. This had led to the assumption that cortical inputs to the basal ganglia encode sensorimotor states rather than reward or choice signals. We tested this hypothesis by studying the coding properties of neurons in the frontal eye field of monkeys that were optogenetically identified as being connected to the basal ganglia. We found that neurons already contained information about expected rewards and selected actions. Further, the reward and condition-independent modulations were stronger in connected neurons than in other neurons in the same area. These findings indicate that reward, choice, and sensorimotor information are integrated already in the inputs to the basal ganglia, implying that the basal ganglia play a role in manipulating rather than generating reward and choice signals.

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A neural basis for flexible perceptual inference

What seems obvious in one context can take on an entirely different meaning if that context shifts. While context-dependent inference has been widely studied, a fundamental question remains: how does the brain simultaneously infer both the meaning of sensory input and the underlying context itself, especially when the context is changing? Here, we study flexible perceptual inference--the ability to adapt rapidly to implicit contextual shifts without trial and error. We introduce a novel change-detection task in dynamic environments that requires tracking latent state and context. We find that mice exhibit first-trial behavioral adaptation to latent context shifts driven by inference rather than reward feedback. By deriving the Bayes-optimal policy under a partially observable Markov decision process, we show that rapid adaptation emerges from sequential updates of an internal belief state. In addition, we show that artificial neural networks trained via reinforcement learning achieve near-optimal performance, implementing Bayesian inference-like mechanisms within their recurrent dynamics. These networks develop flexible internal representations that enable real-time adjustments to the inference model. Our findings establish flexible perceptual inference as a core principle of cognitive flexibility, offering computational and neural-mechanistic insights into adaptive behavior in uncertain environments.

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Inference based decisions in a hidden state foraging task: differential contributions of prefrontal cortical areas

Essential features of the world are often hidden and must be inferred by constructing internal models based on indirect evidence. Here, to study the mechanisms of inference we established a foraging task that is naturalistic and easily learned, yet can distinguish inference from simpler strategies such as the direct integration of sensory data. We show that both mice and humans learn a strategy consistent with optimal inference of a hidden state. However, humans acquire this strategy more than an order of magnitude faster than mice. Using optogenetics in mice we show that orbitofrontal and anterior cingulate cortex inactivation impact task performance, but only orbitofrontal inactivation reverts mice from an inference-based to a stimulus-bound decision strategy. These results establish a cross-species paradigm for studying the problem of inference-based decision-making and begin to dissect the network of brain regions crucial for its performance.

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Activation of serotonin neurons promotes active exploitation in a probabilistic foraging task

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. For example, activation of 5-HT neurons promotes waiting for delayed rewards. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose poke in order to exploit a given site. We found that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increased the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function.

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