There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit. There are strong excitatory connections laterally within the septo-temporally organized lamella and inhibitory trans-lamellar connections in the hippocampus, which allow testing of the connectivity hypothesis. We further tested whether epileptogenesis enhances synchrony and antiseizure drug administration disrupts it. We recorded local field potentials from CA1 pyramidal neurons using a small microelectrode array and kindled rats by a rapid, recurrent hippocampal stimulation protocol. We compared cross-correlation, theta phase synchronization, entropy, and event synchronization. These analyses revealed that the firing pattern was correlated alo...

Acetaldehyde, the first metabolite of ethanol, is implicated in several of ethanol’s actions, including the reinforcing and aversive effects. The neuronal mechanisms underlying acetaldehyde’s aversive effect, however, are poorly understood. The lateral habenula (LHb), a regulator of midbrain monoaminergic centers, is activated by negative valence events. Although the LHb has been linked to the aversive responses of several abused drugs, including ethanol, little is known about acetaldehyde. We, therefore, assessed acetaldehyde’s action on LHb neurons in rats. The results showed that intraperitoneal injection of acetaldehyde increased cFos protein expression within the LHb and that intra-LHb infusion of acetaldehyde induced conditioned place aversion in male rats. Furthermore, electrophysiological recording in brain slices of male and female rats showed that bath application of acetaldehyde facilitated spontaneous firing and glutamatergic transmission. This effect of acetaldehyde was potentiated by an aldeh...

The ventral pallidum (VP) is the major downstream nucleus of the nucleus accumbens (NAc). Both VP and NAc neurons are responsive to reward-predictive stimuli and are critical drivers of reward-seeking behavior. The cue-evoked excitations and inhibitions of NAc neurons predict the vigor (latency and speed) of the cue-elicited locomotor approach response and encode the animal’s proximity to the movement target, but do not encode more specific movement features such as turn direction. VP neurons also encode certain vigor parameters, but it remains unknown whether they also encode more specific movement features, and whether such encoding could account for vigor encoding. To address these questions, we recorded the firing of neurons in the VP of freely moving male rats performing a discriminative stimulus task. Similar to NAc neurons, VP neurons’ cue-evoked excitations were correlated with the speed of the upcoming approach movement and the animal’s proximity to the movement target at cue onset. Unlike NAc neu...

Bombesin receptor subtype-3 (BRS3) is an orphan receptor that regulates energy homeostasis. We compared Brs3 driver mice with constitutive or inducible Cre recombinase activity. The constitutive BRS3-Cre mice show reporter signal (Cre-dependent tdTomato) in the adult brain due to lineage tracing in the dentate gyrus, striatal patches, and indusium griseum, in addition to sites previously identified in the inducible BRS3-Cre mice (including hypothalamic and amygdala subregions, and parabrachial nucleus). We detected Brs3 reporter expression in the dentate gyrus at day 23 but not at postnatal day one or five months of age. Hypothalamic sites expressed reporter at all three time points, and striatal patches expressed Brs3 reporter at one day but not five months. Parabrachial nucleus Brs3 neurons project to the preoptic area, hypothalamus, amygdala, and thalamus. Both Cre recombinase insertions reduced Brs3 mRNA levels and BRS3 function, causing obesity phenotypes of different severity. These results demonstra...

Although composing two words into a complex representation (e.g., “coffee cake”) is conceptually different from forming associations between a pair of words (e.g., “coffee, cake”), the brain regions supporting semantic composition have also been implicated for associative encoding. Here, we adopted a two-word magnetoencephalography (MEG) paradigm which varies compositionality (“French/Korean cheese” vs “France/Korea cheese”) and strength of association (“France/French cheese” vs “Korea/Korean cheese”) between the two words. We collected MEG data while 42 English speakers (24 females) viewed the two words successively in the scanner, and we applied both univariate regression analyses and multivariate pattern classification to the source estimates of the two words. We show that the left anterior temporal lobe (LATL) and left middle temporal lobe (LMTL) are distinctively modulated by semantic composition and semantic association. Specifically, the LATL is mostly sensitive to high-association compositional phr...

Critical decisions, such as in domains ranging from medicine to finance, are often made under threatening circumstances that elicit stress and anxiety. The negative effects of such reactions on learning and decision-making have been repeatedly underscored. In contrast, here we show that perceived threat alters the process by which evidence is accumulated in a way that may be adaptive. Participants ( n = 91) completed a sequential evidence sampling task in which they were incentivized to accurately judge whether they were in a desirable state, which was associated with greater rewards than losses, or an undesirable state, which was associated with greater losses than rewards. Before the task participants in the “threat group” experienced a social-threat manipulation. Results show that perceived threat led to a reduction in the strength of evidence required to reach an undesirable judgment. Computational modeling revealed this was because of an increase in the relative rate by which negative information was ...

N -methyl-d-aspartate receptors (NMDARs) are important for synaptic plasticity associated with many physiological functions and neurologic disorders. Protein kinase C (PKC) activation increases the phosphorylation and activity of NMDARs, and α2δ-1 is a critical NMDAR-interacting protein and controls synaptic trafficking of NMDARs. In this study, we determined the relative roles of PKC and α2δ-1 in the control of NMDAR activity. We found that α2δ-1 coexpression significantly increased NMDAR activity in HEK293 cells transfected with GluN1/GluN2A or GluN1/GluN2B. PKC activation with phorbol 12-myristate 13-acetate (PMA) increased receptor activity only in cells coexpressing GluN1/GluN2A and α2δ-1. Remarkably, PKC inhibition with Gӧ6983 abolished α2δ-1-coexpression-induced potentiation of NMDAR activity in cells transfected with GluN1/GluN2A or GluN1/GluN2B. Treatment with PMA increased the α2δ-1–GluN1 interaction and promoted α2δ-1 and GluN1 cell surface trafficking. PMA also significantly increased NMDAR act...

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology. SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, ...

Current models of object recognition are based on spatial representations build from object features that are simultaneously present in the retinal image. However, one can recognize an object when it moves behind a static occlude, and only a small fragment of its shape is visible through a slit at a given moment in time. Such anorthoscopic perception requires spatiotemporal integration of the successively presented shape parts during slit-viewing. Human fMRI studies suggested that ventral visual stream areas represent whole shapes formed through temporal integration during anorthoscopic perception. To examine the time course of shape-selective responses during slit-viewing, we recorded the responses of single inferior temporal (IT) neurons of rhesus monkeys to moving shapes that were only partially visible through a static narrow slit. The IT neurons signaled shape identity by their response when that was cumulated across the duration of the shape presentation. Their shape preference during slit-viewing eq...