Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-G...

Evidence from animal and human research shows that established memories can undergo changes after reactivation through a process called reconsolidation. Alterations of the level of the stress hormone cortisol may provide a way to manipulate reconsolidation in humans. Here, in a double-blind, within-subject design, we reactivated a 3-d-old memory at 3:55 A.M. in sixteen men and four women, immediately followed by oral administration of metyrapone versus placebo, to examine whether metyrapone-induced suppression of the morning cortisol rise may influence reconsolidation processes during and after early morning sleep. Crucially, reactivation followed by cortisol suppression versus placebo resulted in enhanced memory for the reactivated episode tested 4 d after reactivation. This enhancement after cortisol suppression was specific for the reactivated episode versus a non-reactivated episode. These findings suggest that when reactivation of memories is immediately followed by suppression of cortisol levels duri...

The human brain continuously processes streams of visual input. Yet, a single image typically triggers neural responses that extend beyond 1s. To understand how the brain encodes and maintains successive images, we analyzed with electroencephalography the brain activity of human subjects while they watched ∼5000 visual stimuli presented in fast sequences. First, we confirm that each stimulus can be decoded from brain activity for ∼1s, and we demonstrate that the brain simultaneously represents multiple images at each time instant. Second, we source localize the corresponding brain responses in the expected visual hierarchy and show that distinct brain regions represent, at each time instant, different snapshots of past stimulations. Third, we propose a simple framework to further characterize the dynamical system of these traveling waves. Our results show that a chain of neural circuits, which each consist of (1) a hidden maintenance mechanism and (2) an observable update mechanism, accounts for the dynami...

Despina Antypa, Aurore A. Perrault, Patrik Vuilleumier, Sophie Schwartz, and Ulrike Rimmele (see pages [7259–7266][1]) Newly encoded memories are strengthened and stabilized for long-term retention through a process called consolidation. Consolidated memories are not immutable, however. Each

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. Th...

Natural scenes deliver rich sensory information about the world. Decades of research has shown that the scene-selective network in the visual cortex represents various aspects of scenes. However, less is known about how such complex scene information is processed beyond the visual cortex, such as in the prefrontal cortex. It is also unknown how task context impacts the process of scene perception, modulating which scene content is represented in the brain. In this study, we investigate these questions using scene images from four natural scene categories, which also depict two types of scene attributes, temperature (warm or cold), and sound level (noisy or quiet). A group of healthy human subjects from both sexes participated in the present study using fMRI. In the study, participants viewed scene images under two different task conditions: temperature judgment and sound-level judgment. We analyzed how these scene attributes and categories are represented across the brain under these task conditions. Our f...

The striatum plays critical roles in visually-guided decision-making and receives dense axonal projections from midbrain dopamine neurons. However, the roles of striatal dopamine in visual decision-making are poorly understood. We trained male and female mice to perform a visual decision task with asymmetric reward payoff, and we recorded the activity of dopamine axons innervating striatum. Dopamine axons in the dorsomedial striatum (DMS) responded to contralateral visual stimuli and contralateral rewarded actions. Neural responses to contralateral stimuli could not be explained by orienting behavior such as eye movements. Moreover, these contralateral stimulus responses persisted in sessions where the animals were instructed to not move to obtain reward, further indicating that these signals are stimulus-related. Lastly, we show that DMS dopamine signals were qualitatively different from dopamine signals in the ventral striatum (VS), which responded to both ipsilateral and contralateral stimuli, conformin...

Molecular, anatomic, and behavioral studies show that the hippocampus is structurally and functionally heterogeneous, with dorsal hippocampus implicated in mnemonic processes and spatial navigation and ventral hippocampus involved in affective processes. By performing electrophysiological recordings of large neuronal populations in dorsal and ventral CA1 in head-fixed mice navigating a virtual environment, we found that this diversity resulted in different strategies for population coding of space. Populations of neurons in dorsal CA1 showed more complex patterns of activity, which resulted in a higher dimensionality of neural representations that translated to more information being encoded, as compared ensembles in vCA1. Furthermore, a pairwise maximum entropy model was better at predicting the structure of these global patterns of activity in ventral CA1 as compared to dorsal CA1. Taken together, the different coding strategies we uncovered likely emerge from anatomical and physiological differences alo...

Hippocampus and prefrontal cortex (PFC) circuits are thought to play a prominent role in human episodic memory, but the precise nature, and electrophysiological basis, of directed information flow between these regions and their role in verbal memory formation has remained elusive. Here we investigate nonlinear causal interactions between hippocampus and lateral PFC using intracranial EEG recordings (from both sexes) during verbal memory encoding and recall tasks. Direction-specific information theoretic analysis revealed higher causal information flow from the hippocampus to PFC than in the reverse direction. Crucially, this pattern was observed during both memory encoding and recall, and the strength of causal interactions was significantly greater during memory task performance than resting baseline. Further analyses revealed frequency-specificity of interactions with greater causal information flow from hippocampus to the PFC in the delta-theta frequency band (0.5-8 Hz); in contrast, PFC to hippocampus...

Hearing in noise is a problem often assumed to depend on encoding of energy level by channels tuned to target frequencies, but few studies have tested this hypothesis. The present study examined neural correlates of behavioral tone-in-noise (TIN) detection in budgerigars ( Melopsittacus undulatus , either sex), a parakeet species with human-like behavioral sensitivity to many simple and complex sounds. Behavioral sensitivity to tones in band-limited noise was assessed using operant-conditioning procedures. Neural recordings were made in awake animals from midbrain-level neurons in the inferior colliculus, the first processing stage of the ascending auditory pathway with pronounced rate-based encoding of stimulus amplitude modulation. Budgerigar TIN detection thresholds were similar to human thresholds across the full range of frequencies (0.5–4 kHz) and noise levels (45–85 dB SPL) tested. Also as in humans, thresholds were minimally affected by a challenging roving-level condition with random variation in ...