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Beïque, J.-C.

Publications and source records attributed to Beïque, J.-C..

4 recordsLinked to original sources

Serotonin predictively encodes value

The in vivo responses of dorsal raphe nucleus (DRN) serotonin neurons to emotionally-salient stimuli are a puzzle. Existing theories centred on reward, surprise, or uncertainty individually account for some aspects of serotonergic activity but not others. Here we find a unifying perspective in a biologically-constrained predictive code for cumulative future reward, a quantity called state value in reinforcement learning. Through simulations of trace conditioning experiments common in the serotonin literature, we show that our theory, called value prediction, intuitively explains phasic activation by both rewards and punishments, preference for surprising rewards but absence of a corresponding preference for punishments, and contextual modulation of tonic firing--observations that currently form the basis of many and varied serotonergic theories. Next, we re-analyzed data from a recent experiment and found serotonin neurons with activity patterns that are a surprisingly close match: our theory predicts the marginal effect of reward history on population activity with a precision <<0.1 Hz neuron-1. Finally, we directly compared against quantitative formulations of existing ideas and found that our theory best explains both within-trial activity dynamics and trial-to-trial modulations, offering performance usually several times better than the closest alternative. Overall, our results show that previous models are not wrong, but incomplete, and that reward, surprise, salience, and uncertainty are simply different faces of a predictively-encoded value signal. By unifying previous theories, our work represents an important step towards understanding the potentially heterogeneous computational roles of serotonin in learning, behaviour, and beyond.

neuroscience↗

Cellular Substrate of Eligibility Traces

The ability of synapses to undergo associative, activity-dependent weight changes constitutes a linchpin of current cellular models of learning and memory. It is, however, unclear whether canonical forms of Hebbian plasticity, which inherently detect correlations of cellular events occurring over short time scales, can solve the temporal credit assignment problem proper to learning driven by delayed behavioral outcomes. Recent evidence supports the existence of synaptic eligibility traces, a time decaying process that renders synapses momentarily eligible for a weight update by a delayed instructive signal. While eligibility traces offer a means of retrospective credit assignment, their material nature is unknown. Here, we combined whole-cell recordings with two-photon uncaging, calcium imaging and biophysical modeling to address this question. We observed and parameterized a form of behavioral timescale synaptic plasticity (BTSP) in layer 5 pyramidal neurons of mice prefrontal areas wherein the pairing of temporally separated pre- and postsynaptic events (0.5 s - 1 s), irrespective of order, induced synaptic potentiation. By imaging calcium in apical oblique dendrites, we reveal a short-term and associative plasticity of calcium dynamics (STAPCD) whose time-dependence mirrored the induction rules of BTSP. We identified a core set of molecular players that were essential for both STAPCD and BTSP and that, together with computational simulations, support a model wherein the dynamics of intracellular handling of calcium by the endoplasmic reticulum (ER) provides a latent memory trace of neural activity that instantiates synaptic weight updates upon a delayed instructive signal. By satisfying the requirements expected of eligibility traces, this mechanism accounts for how individual neurons can conjunctively bind cellular events that are separated by behaviorally relevant temporal delays, and thus offers a cellular model of reinforced learning.

neuroscience↗

Temporal derivative computation in the dorsal raphe network revealed by an experimentally-driven augmented integrate-and-fire modeling framework

By means of an expansive innervation, the serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) are positioned to enact coordinated modulation of circuits distributed across the entire brain in order to adaptively regulate behavior. Yet the network computations that emerge from the excitability and connectivity features of the DRN are still poorly understood. To gain insight into these computations, we began by carrying out a detailed electrophysiological characterization of genetically-identified mouse 5-HT and somatostatin (SOM) neurons. We next developed a single-neuron modeling framework that combines the realism of Hodgkin-Huxley models with the simplicity and predictive power of generalized integrate-and-fire (GIF) models. We found that feedforward inhibition of 5-HT neurons by heterogeneous SOM neurons implemented divisive inhibition, while endocannabinoid-mediated modulation of excitatory drive to the DRN increased the gain of 5-HT output. Our most striking finding was that the output of the DRN encodes a mixture of the intensity and temporal derivative of its input, and that the temporal derivative component dominates this mixture precisely when the input is increasing rapidly. This network computation primarily emerged from prominent adaptation mechanisms found in 5-HT neurons, including a previously undescribed dynamic threshold. By applying a bottom-up neural network modeling approach, our results suggest that the DRN is particularly apt to encode input changes over short timescales, reflecting one of the salient emerging computations that dominate its output to regulate behavior.

neuroscience↗

Parsing out the variability of transmission at central synapses using optical quantal analysis

Properties of synaptic release dictates the core of information transfer in neural circuits. Despite decades of technical and theoretical advances, distinguishing bona fide information content from the multiple sources of synaptic variability remains a challenging problem. Here, we employed a combination of computational approaches with cellular electrophysiology, two-photon uncaging of MNI-Glutamate and imaging at single synapses. We describe and calibrate the use of the fluorescent glutamate sensor iGluSnFR and found that its kinetic profile is close to that of AMPA receptors, therefore providing several distinct advantages over slower methods relying on NMDA receptor activation (i.e., chemical or genetically encoded Calcium indicators). Using an array of statistical methods, we further developed, and validated on surrogate data, an expectation-maximization algorithm that, by biophysically constraining release variability, extracts the quantal parameters n (maximum number of released vesicles) and p (unitary probability of release) from single-synapse iGluSnFR-mediated transients. Together, we present a generalizable mathematical formalism which, when applied to optical recordings, paves the way to an increasingly precise investigation of information transfer at central synapses.

neuroscience↗