Theta-scale coordination of prelimbic medial prefrontal cortex (mPFC) local field potentials (LFPs) and its influence via direct or indirect projections to the ventral hippocampus (vHC) and dorsal hippocampus (dHC) during spatial learning remains poorly understood. We hypothesized that theta frequency coordination dynamics within and between the mPFC, dHC and vHC would be predetermined by the level of connectivity rather than reflecting differing circuit throughput relationships depending on cognitive demands. Moreover, we hypothesized that coherence levels would not change during learning of a complex spatial avoidance task. Adult male rats were bilaterally implanted with EEG electrodes and LFPs recorded in each structure. Contrary to predictions, theta coherence averaged across ‘Early’ or ‘Late’ training sessions in the mPFC-HC, mPFC-mPFC, and HC-HC increased as a function of task learning. Coherence levels were also highest between the indirectly connected mPFC-dHC circuit, particularly during early tra...

Tools for refined cell-specific targeting have significantly contributed to understanding the characteristics and dynamics of distinct cellular populations by brain region. While advanced cell-labeling methods have accelerated the field of neuroscience, specifically in brain mapping, there remains a need to quantify and analyze the data. Here, by modifying a toolkit that localizes electrodes to brain regions (SHARP-Track), we introduce a post-imaging analysis tool to map histological images to established mouse brain atlases called SHARCQ (Slice Histology Alignment, Registration, and Cell Quantification). The program requires MATLAB, histological images, and either a manual or automatic cell count of the unprocessed images. SHARCQ simplifies the post-imaging analysis pipeline with a step-by-step GUI. We demonstrate that SHARCQ can be applied for a variety of mouse brain images, regardless of histology technique. In addition, SHARCQ rectifies discrepancies in mouse brain region borders between atlases by al...

Inducible Cre recombinase facilitates temporal control of genetic recombination in numerous transgenic model systems, a feature which has made it a popular tool for adult neurogenesis studies. One of the most common forms of inducible Cre, CreERT2, requires activation by the selective estrogen receptor modulator tamoxifen (TAM) to initiate recombination of LoxP-flanked sequences. To date, most studies deliver TAM via intraperitoneal injection. But the introduction of TAM-infused commercial chows has recently expanded the possible modes of TAM delivery. Despite the widespread use of TAM-inducible genetic models in adult neurogenesis research, the comparative efficiency and off-target effects of TAM administration protocols is surprisingly infrequently studied. Here we compare a standard, 5 day TAM injection regimen with voluntary consumption of TAM-infused chow. First, we used adult NestinCreERT2;Rosa-LoxP-STOP-LoxP-EYFP reporter mice to show that 2 weeks of TAM chow and 5 days of injections led to LoxP rec...

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA–ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the exci...

Mossy cells (MCs) of the dentate gyrus are key components of an excitatory associative circuit established by reciprocal connections with dentate granule cells (GCs). MCs are implicated in place field encoding, pattern separation, and novelty detection, as well as in brain disorders such as temporal lobe epilepsy and depression. Despite their functional relevance, little is known about the determinants that control MC activity. Here, we examined whether MCs express functional kainate receptors (KARs), a subtype of glutamate receptors involved in neuronal development, synaptic transmission, and epilepsy. Using mouse hippocampal slices, we found that bath application of submicromolar and micromolar concentrations of the KAR agonist kainic acid induced inward currents and robust MC firing. These effects were abolished in GluK2 KO mice, indicating the presence of functional GluK2-containing KARs in MCs. In contrast to CA3 pyramidal cells, which are structurally and functionally similar to MCs and express synap...

Oxytocin (OXT) neurons in paraventricular nucleus of hypothalamus (PVN) are involved in modulating multiple functions, including social, maternal, feeding, and emotional related behaviors. PVN OXT neurons are canonically classified into magnocellular (Magno) and parvocellular (Parvo) subtypes. However, morpho-electric properties and the diversity of PVN OXT neurons are not well investigated. In this study, we profiled the morpho-electric properties of PVN OXT neurons by combining transgenic mice, electrophysiological recording, morphologic reconstruction, and unsupervised clustering analyses. Total 224 PVN OXT neurons from 23 mice were recorded and used for analyses in this study, and 29 morpho-electric parameters were measured. Magno and Parvo OXT neurons have prominent differences in their morpho-electric features, and PVN OXT neurons in male and female mice share similar neuronal properties. Some morpho-electric features of PVN OXT neurons, especially Magno neurons, exhibit significant diverse changes a...

Overlap between events can lead to interference because of a trade-off between encoding the present event and retrieving the past event. Temporal context information, “when” something occurred, a defining feature of episodic memory, can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference is unclear. Here, by identifying brain states using scalp EEG from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification analy...

Researchers generally agree that when upregulating and downregulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating brain areas. However, the “affective dial hypothesis” that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We tested this hypothesis by examining the overlap between the regions activated during upregulation and those deactivated during downregulation in 54 male and 51 female humans. We found that upregulation and downregulation both recruit regulatory regions, such as the inferior frontal gyrus and dorsal anterior cingulate gyrus, but act on distinct affect-generating regions. Upregulation increased activity in regions associated with emotional experience, such as the amygdala, anterior insula, striatum, and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity, such as periventricular white matter, while downregulation decreased activity in regio...

Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, et al. (see pages [2872–2884][1]) Hilar mossy cells (MCs) are part of the hippocampal circuitry that helps organisms detect locations, patterns and novel stimuli, and their dysfunction is implicated in epilepsy and