Persistent avoidance of stress-related stimuli following acute stress exposure predicts negative outcomes such as substance abuse and traumatic stress disorders. Previous work using a rat model showed that the central amygdala (CeA) plays an important role in avoidance of a predator odor stress-paired context. Here, we show that CeA projections to the lateral hypothalamus (LH) are preferentially activated in male rats that show avoidance of a predator odor-paired context (termed Avoider rats), that chemogenetic inhibition of CeA-LH projections attenuates avoidance in male Avoider rats, that chemogenetic stimulation of the CeA-LH circuit produces conditioned place avoidance (CPA) in otherwise naive male rats, and that avoidance behavior is associated with intrinsic properties of LH-projecting CeA cells. Collectively, these data show that CeA-LH projections are important for persistent avoidance of stress-related stimuli following acute stress exposure. SIGNIFICANCE STATEMENT This study in rats shows that a...

Aggression is a complex social behavior that is necessary for survival and protecting territories/resources but can be destructive when it is expressed inappropriately. Short-term escalation in aggression is observed in many species, including humans, after an initial exposure to a conspecific

Clinical µ-opioid receptor (MOR) agonists produce hyperalgesic priming, a form of maladaptive nociceptor neuroplasticity, resulting in pain chronification. We have established an in vitro model of opioid-induced hyperalgesic priming (OIHP), in male rats, to identify nociceptor populations involved and its maintenance mechanisms. OIHP was induced in vivo by systemic administration of fentanyl and confirmed by prolongation of prostaglandin E2 (PGE2) hyperalgesia. Intrathecal cordycepin, which reverses Type I priming, or the combination of Src and mitogen-activated protein kinase (MAPK) inhibitors, which reverses Type II priming, both partially attenuated OIHP. Parallel in vitro experiments were performed on small-diameter (<30 µm) dorsal root ganglion (DRG) neurons, cultured from fentanyl-primed rats, and rats with OIHP treated with agents that reverse Type I or Type II priming. Enhancement of the sensitizing effect of a low concentration of PGE2 (10 nm), another characteristic feature of priming, measured a...

Humans can vividly recall and re-experience events from their past, and these are commonly referred to as episodic or autobiographical memories. fMRI experiments reliably associate autobiographical event recall with activity in a network of “default” or “core” brain regions. However, as prior studies have relied on covert (silent) recall procedures, current understanding may be hampered by methodological limitations that obscure dynamic effects supporting moment-to-moment content retrieval. Here, fMRI participants ( N = 40) overtly (verbally) recalled memories for ∼2 min periods. The content of spoken descriptions was categorized using a variant of the Autobiographical Interview (AI) procedure ([Levine et al., 2002][1]) and temporally re-aligned with BOLD data so activity accompanying the recall of different details could be measured. Replicating prior work, sustained effects associated with autobiographical recall periods (which are insensitive to the moment-to-moment content of retrieval) fell primarily ...

Prior knowledge profoundly influences perceptual processing. Previous studies have revealed consistent suppression of predicted stimulus information in sensory areas, but how prior knowledge modulates processing higher up in the cortical hierarchy remains poorly understood. In addition, the mechanism leading to suppression of predicted sensory information remains unclear, and studies thus far have revealed a mixed pattern of results in support of either the “sharpening” or “dampening” model. Here, using 7T fMRI in humans (both sexes), we observed that prior knowledge acquired from fast, one-shot perceptual learning sharpens neural representation throughout the ventral visual stream, generating suppressed sensory responses. In contrast, the frontoparietal and default mode networks exhibit similar sharpening of content-specific neural representation, but in the context of unchanged and enhanced activity magnitudes, respectively: a pattern we refer to as “selective enhancement.” Together, these results reveal...

Neurons are the “delicate and elegant…butterflies of the soul,” as Santiago Ramón y Cajal famously put it in his memoir ([Zwirn, 2015][1]). Neurons interconnect throughout the brain and body via the elaborate arborization of their dendrites and axon. Their cytoskeleton, the intricate array of

Loss of auditory-nerve (AN) afferent cochlear innervation is a prevalent human condition that does not affect audiometric thresholds and therefore remains largely undetectable with standard clinical tests. AN loss is widely expected to cause hearing difficulties in noise, known as “hidden hearing loss,” but support for this hypothesis is controversial. Here, we used operant conditioning procedures to examine the perceptual impact of AN loss on behavioral tone-in-noise (TIN) sensitivity in the budgerigar ( Melopsittacus undulatus ; of either sex), an avian animal model with complex hearing abilities similar to humans. Bilateral kainic acid (KA) infusions depressed compound AN responses by 40–70% without impacting otoacoustic emissions or behavioral tone sensitivity in quiet. Surprisingly, animals with AN damage showed normal thresholds for tone detection in noise (0.1 ± 1.0 dB compared to control animals; mean difference ± SE), even under a challenging roving-level condition with random stimulus variation a...

The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons that aid in distinguishing between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HCs) share structural, functional, and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Because of these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic acetylcholine receptor (nAChR). However, the identities of the molecular players underlying ACh-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not the α10, subunits are enriched in zebrafish HCs. Moreover, the heterologous expression...

The capacity for sensory systems to encode relevant information that is invariant to many stimulus changes is central to normal, real-world, cognitive function. This invariance is thought to be reflected in the complex spatiotemporal activity patterns of neural populations, but our understanding of population-level representational invariance remains coarse. Applied topology is a promising tool to discover invariant structure in large datasets. Here, we use topological techniques to characterize and compare the spatiotemporal pattern of coactive spiking within populations of simultaneously recorded neurons in the secondary auditory region caudal medial neostriatum of European starlings ( Sturnus vulgaris ). We show that the pattern of population spike train coactivity carries stimulus-specific structure that is not reducible to that of individual neurons. We then introduce a topology-based similarity measure for population coactivity that is sensitive to invariant stimulus structure and show that this meas...

Functional connectivity of neural oscillations (oscillation-based FC) is thought to afford dynamic information exchange across task-relevant neural ensembles. Although oscillation-based FC is classically defined relative to a prestimulus baseline, giving rise to rapid, context-dependent changes in individual connections, studies of distributed spatial patterns show that oscillation-based FC is omnipresent, occurring even in the absence of explicit cognitive demands. Thus, the issue of whether oscillation-based FC is primarily shaped by cognitive state or is intrinsic in nature remains open. Accordingly, we sought to reconcile these observations by interrogating the ECoG recordings of 18 presurgical human patients (8 females) for state dependence of oscillation-based FC in five canonical frequency bands across an array of six task states. FC analysis of phase and amplitude coupling revealed a highly similar, largely state-invariant (i.e., intrinsic) spatial component across cognitive states. This spatial or...