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...

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...

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

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...

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiologic analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies reveal that Med12 regula...

Up states are the best studied example of an emergent neural dynamic regime. Computational models based on a single class of inhibitory neurons indicate that Up states reflect bistable dynamic systems in which positive feedback is stabilized by strong inhibition and predict a paradoxical effect in which increased drive to inhibitory neurons results in decreased inhibitory activity. To date, however, computational models have not incorporated empirically defined properties of parvalbumin (PV) and somatostatin (SST) neurons. Here we first experimentally characterized the frequency–current ( F–I ) curves of pyramidal (Pyr), PV, and SST neurons from mice of either sex, and confirmed a sharp difference between the threshold and slopes of PV and SST neurons. The empirically defined F–I curves were incorporated into a three-population computational model that simulated the empirically derived firing rates of pyramidal, PV, and SST neurons. Simulations revealed that the intrinsic properties were sufficient to pred...

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC–BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental c...

Previously, studies using human neuroimaging and excitotoxic lesions in non-human primate have demonstrated an important role of ventrolateral prefrontal cortex (vlPFC) in higher order cognitive functions such as cognitive flexibility and the planning of behavioral sequences. In the present experiments, we tested effects on performance of temporary inactivation (using GABA receptor agonists) and dopamine (DA) D2 and 5-HT2A-receptor (R) blockade of vlPFC via local intracerebral infusions in the marmoset. We trained common marmosets to perform spatial self-ordered sequencing tasks in which one cohort of animals performed two and three response sequences on a continuously varying spatial array of response options on a touch-sensitive screen. Inactivation of vlPFC produced a marked disruption of accuracy of sequencing which also exhibited significant error perseveration. There were somewhat contrasting effects of D2 and 5-HT2A-R blockade, with the former producing error perseveration on incorrect trials, thoug...