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Teboul, E.

Publications and source records attributed to Teboul, E..

6 recordsLinked to original sources

An Amygdalar Oscillatory Switch Governs Valence Assignment

Reward pursuit and punishment avoidance are among the most fundamental behaviors necessary for survival. The binary valuation of an experience as either positive or negative - "valence assignment" - is imperative for successful navigation of a regularly updating environment. Mounting evidence highlights the critical role of valence responsive basolateral amygdala (BLA) ensembles in coding valence information. However, how BLA ensembles are recruited to drive real-time valence assignment remains elusive. Here, we show locus coeruleus (LC)-derived norepinephrine coordinates this neural computational process via modulatory control over network-organizing BLA parvalbumin-expressing (PV) interneuron activity. Specifically, optogenetic activation of LC to BLA noradrenergic terminals (LC-BLANE) drives real-time negative valence assignment and suppression of BLA fast gamma oscillatory activity via BLA interneuronal 1a adrenergic receptor signaling. Conversely, positive valence assignment also requires BLA PV interneuron activity but is associated with an enhancement of local fast gamma power. Together, these converging data highlight a PV-driven amygdalar oscillatory switch that governs valence assignment.

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Early life stress impairs VTA coordination of BLA network and behavioral states

Motivated behaviors, such as social interactions, are governed by the interplay between mesocorticolimbic structures, such as the ventral tegmental area (VTA), basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adverse childhood experiences and early life stress (ELS) can impact these networks and behaviors, which is associated with increased risk for psychiatric illnesses. While it is known that the VTA projects to both the BLA and mPFC, the influence of these inputs on local network activity which govern behavioral states - and whether ELS impacts VTA-mediated network communication - remains unknown. Our study demonstrates that VTA inputs influence BLA oscillations and mPFC activity, and that ELS weakens the ability of the VTA to coordinate BLA network states, likely due to ELS-induced impairments in dopamine signaling between the VTA and BLA. Consequently, ELS mice exhibit increased social avoidance, which can be recapitulated in control mice by inhibiting VTA-BLA communication. These data suggest that ELS impacts social reward via the VTA-BLA dopamine network.

neuroscience↗

Basolateral amygdala parvalbumin interneurons coordinate oscillations to drive reward behaviors

The basolateral amygdala (BLA) has been implicated in mediating both fear and reward learning. Parvalbumin interneurons (PVs) in the BLA have previously been shown to contribute to BLA oscillatory states integral to fear expression, but whether BLA oscillatory states and PV interneurons also contribute to reward learning is unknown and critical to our understanding of reward processing. Local field potentials in the BLA were collected as animals consumed a sucrose reward, where prominent changes in the beta band (15-30 Hz) emerged with reward experience. Rhythmic optogenetic stimulation of PV interneurons to entrain the BLA network to 20Hz during consumption of one bottle during a two-bottle choice test produced a robust bottle preference. Finally, to demonstrate that PV activity is necessary for reward value use, PVs were chemogenetically targeted and inhibited following outcome devaluation, rendering those animals incapable of using updated reward value information to guide their behavior. Taken together, these experiments provide novel information regarding the physiological signatures of reward learning while highlighting the importance of PV interneurons in reward learning. This work builds upon the fields established knowledge of PV involvement in fear expression and provides evidence that PV orchestration of unique BLA network states is involved in both learning types.

neuroscience↗

Neuromodulation-induced burst firing in parvalbumin interneurons of the basolateral amygdala mediates transition between fear-associated network and behavioral states

Patterned coordination of network activity in the basolateral amygdala (BLA) is important for fear expression. Neuromodulatory systems play an essential role in regulating changes between behavioral states, however the mechanisms underlying the neuromodulatory control of BLA circuits that mediates transitions between brain and behavioral states remain largely unknown. We examined the role of neuromodulation of parvalbumin (PV)-expressing interneurons in the BLA in coordinating network and behavioral states using combined chemogenetics, ex vivo patch clamp recordings, and in vivo and ex vivo local field potential recordings. We show that Gq signaling, whether by the designer receptor, hM3D, 1A adrenoreceptors, or 5-HT2a serotonergic receptors, induces a previously undescribed, highly stereotyped bursting pattern of activity in BLA PV interneurons that generates synchronous bursts of inhibitory postsynaptic currents and phasic firing in the BLA principal neurons. The Gq activation in PV interneurons induced a transition from tonic to phasic firing in the BLA PV neurons and principal neurons and suppressed BLA gamma oscillations in slices and suppressed BLA gamma and potentiated theta power in vivo. Gq activation in BLA PV interneurons also facilitated fear memory recall, consistent with previous reports of BLA gamma suppression and theta potentiation during conditioned fear expression. Thus, our data reveal a BLA parvalbumin neuron-specific Gq neuromodulatory mechanism that mediates the transition to a fear-associated network and behavioral state.

neuroscience↗

Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, we demonstrate that inhibition of prefrontal parvalbumin-expressing interneurons during the juvenile and adolescent period, results in persistent impairments in adult prefrontal circuit connectivity, in vivo network function and behavioral flexibility that can be reversed by targeted activation of parvalbumin interneurons in adulthood. In contrast, transient suppression of parvalbumin interneuron activity in adulthood produces no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal circuit maturation and highlight how abnormal parvalbumin interneuron activity during development alters adult prefrontal circuit function and cognitive behavior.

neuroscience↗

Dopamine D2 receptors modulate the cholinergic pause and inhibitory learning

Cholinergic interneurons (CINs) in the striatum respond to salient stimuli with a multiphasic response, including a pause, in neuronal activity. Slice physiology experiments have shown the importance of dopamine D2 receptors (D2Rs) in regulating CIN pausing yet the behavioral significance of the CIN pause and its regulation by dopamine in vivo is still unclear. Here, we show that D2R upregulation in CINs of the nucleus accumbens (NAc) lengthens the pause in CIN activity ex vivo and enlarges a stimulus-evoked decrease in acetylcholine (ACh) levels during behavior. This enhanced dip in ACh levels is associated with a selective deficit in the learning to inhibit responding in a Go/No-Go task. Our data demonstrate, therefore, the importance of CIN D2Rs in modulating the CIN response induced by salient stimuli and points to a role of the pause in inhibitory learning. This work has important implications for brain disorders with altered striatal dopamine and ACh function, including schizophrenia and attention-deficit hyperactivity disorder (ADHD).

neuroscience↗