Acute ischemic stroke (AIS) is a severe neurological disease associated with Th17/Treg cell imbalance and dysregulation of the Wnt/β-catenin signaling pathway. This study investigates whether miR-155 inhibition can activate Wnt/β-catenin signaling, improve Th17/Treg balance, and provide neuroprotection against stroke. We conducted a multilevel experimental design, including high-throughput sequencing, bioinformatics analysis, in vivo mouse models, and in vitro cell experiments. High-throughput sequencing revealed significant differential gene expression between the miR-155 antagomir–treated and control groups (BioProject: PRJNA1152758). Bioinformatics analysis identified key genes linked to Wnt/β-catenin signaling and Th17/Treg imbalance. In vitro experiments confirmed that miR-155 inhibition activated Wnt/β-catenin signaling and improved Th17/Treg ratios. In vivo studies demonstrated that miR-155 antagomir treatment provided significant neuroprotection against AIS. These findings suggest that targeting mi...

We were interested in the role that attention might play in disordered thought processes frequent in schizophrenia. Specifically, we wanted to examine the role of reflexive and voluntary attentional processes in the semantic domain by using a category-switching manipulation based on Neely’s 1977 work with normal subjects. Similar to an antisaccade task, he used this category-switching paradigm to separate semantic priming that would occur automatically for a related but unexpected word from semantic priming that would occur for a word from an expected but unrelated category. We tested 19 schizophrenic patients (SzP) on a similar lexical decision task. Probe stimuli were either words from 1 of 2 categories (“Animal” or “Body Part”) or pronounceable nonwords. Prime stimuli were the words “Animal,” “Body Part,” or “Neutral”. SzP were told that when the prime word was “Animal” or “Body Part,” then 80% of the time, the following probe would be a word from the opposite category (i.e. Body Part or Animal, respect...

There are distinct neural pathways subserving memory-guided behavior, such as mnemonic discrimination, with item/object memory depending more strongly on perirhinal cortex (PRC) and lateral entorhinal cortex (LEC), while scene/context memory mainly invo...

While much of memory research takes a subject-centric focus, recent work has also pinpointed important item-centric effects on memory, driven by how intrinsically memorable or forgettable a stimulus is. Specifically, recent neuroimaging research finds t...

Elder subjects are capable of priming on an object decision task. However, in contrast to young adults who continue to prime 1 week later, elders can no longer prime after a 20 minute delay. We hypothesized that there would be processing differences during initial exposure to the material between the 2 groups. In an ERfMRI study, 12 young and 10 old subjects had 2 exposure sessions for possible (P) and impossible (I) objects. Subjects then indicated whether intermixed exposed and non-exposed objects were P or I. Consistent with previous studies, both groups tended to show priming on this decision for P, but not I objects. For the fMRI data obtained during the second exposure sessions, differential activation for P vs I objects (P-I) was correlated (across subjects) with the difference between P and I priming. A statistically significant positive slope for this relationship was observed at the left and right cingulate, superior frontal gyrus, left medial frontal gyrus, middle temporal gyrus, angular gyrus a...

Growth hormone (GH) is a neuromodulator that binds to receptors in the hippocampus and alters synaptic plasticity. A decline in GH levels is associated with normal aging, stress, and disease, and the mechanisms proposed involve the hippocampal circuit plasticity. To see how GH affects the hippocampal neural code, we recorded single neurons in the CA1 region of male Long–Evans rats with locally altered GH levels. Rats received injections of adeno-associated viruses into the hippocampus to make the cells overexpress either GH or an antagonizing mutated GH (aGH). Place cells were recorded in both familiar and novel environments to allow the assessment of pattern separation in the neural representations termed remapping. All the animals showed intact and stable place fields in the familiar environment. In the novel environment, aGH transfection increased the average firing rate, peak rate, and information density of the CA1 place fields. The tendency of global remapping increased in the GH animals compared wit...

Synaptic vesicle protein 2 (SV2), one of the first synaptic vesicle proteins identified, is characterized by multiple transmembrane regions that exhibit homology to sugar transporters, and by a highly glycosylated intravesicular sequence. Deletion of SV2 causes postnatal lethality in mice, primarily because of fulminant epilepsy. At the cellular level, deletion of SV2 impairs neurotransmitter release, but its function is unknown, and even the exact point at which release is affected in SV2-deleted synapses remains unclear. Using electrophysiological approaches, we now examine at what step in exocytosis the deletion of SV2 impairs release. Our data demonstrate that deletion of SV2 produces a decrease in evoked synaptic responses without causing changes in mini frequency, mini amplitude, the readily releasable pool of vesicles, or the apparent Ca2+ sensitivity of vesicle fusion. These findings indicate that a previously unidentified step may couple priming of synaptic vesicles to Ca2+ triggering of fusion, a...

To gain an understanding of the cognitive and neural mechanisms of object recognition in humans, we need to broadly sample object categories using naturalistic object images and identify sensitive methods for relating them to human behavior. Here we rep...

Analyzing large brain volumes is an acknowledged problem in nanoscale connectomics, and laboratories around the world are beginning to routinely publish datasets in excess of 100TB. IARPA MICrONS is a research program that seeks to improve biofidelic ma...

The increasing incidence of neurological and mental illnesses in the U.S. and worldwide makes it likely that younger students will know someone who has been affected by a disease or disorder of the brain. The high economic costs, emotional and health im...