RJ Wenthold
Mar 15, 1996; 16:1982-1989
Articles

Xiao-Jing Wang
Oct 15, 1996; 16:6402-6413
Articles

KM Harris
Jul 1, 1992; 12:2685-2705
Articles

KM Harris
Aug 1, 1989; 9:2982-2997
Articles

Jasper Akerboom
Oct 3, 2012; 32:13819-13840
Cellular

RU Muller
Jul 1, 1987; 7:1951-1968
Articles

Thomas Schikorski
Aug 1, 1997; 17:5858-5867
Articles

A Bragin
Jan 1, 1995; 15:47-60
Articles

Guo-qiang Bi
Dec 15, 1998; 18:10464-10472
Articles

CG Dotti
Apr 1, 1988; 8:1454-1468
Articles

Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia's pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone.

SIGNIFICANCE STATEMENT NMDAR hypofunction in cortical interneurons has been linked to schizophrenia pathophysiology. How a dysfunction of GABAergic cortical interneurons interacts with maturation during adolescence has not been clarified yet. Here, we demonstrate in vivo that early postnatal ablation of the NMDAR in corticolimbic interneurons results in an overactive but desynchronized PFC before adolescence. Final postnatal maturation during this stage outspreads the impact of the genetic manipulation toward a functional disconnection of the ventral hippocampal-prefrontal pathway, probably as a consequence of an exacerbated propensity toward hippocampal-evoked depotentiation plasticity. Our results demonstrate a complex interaction between genetic and developmental factors affecting cortical interneurons and PFC function.

The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations.

SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning.

The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M₂ or M₄ receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

SIGNIFICANCE STATEMENT The major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to speculation that the septo-hippocampal cholinergic projection contributing to theta oscillation. In this article, by long-term recording of MS cholinergic neurons, we found that they show a theta state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during slow-wave sleep could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M₂ and M₄ receptors.

Persistent alterations in neuronal activity elicit homeostatic plastic changes in synaptic transmission and/or intrinsic excitability. However, it is unknown whether these homeostatic processes operate in concert or at different temporal scales to maintain network activity around a set-point value. Here we show that chronic neuronal hyperactivity, induced by M-channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in cultured hippocampal pyramidal neurons from mice of either sex. Homeostatic changes of intrinsic excitability occurred at a fast timescale (1–4 h) and depended on ongoing spiking activity. This fast intrinsic adaptation included plastic changes in the threshold current and a distal relocation of FGF14, a protein physically bridging Na_v1.6 and K_v7.2 channels along the axon initial segment. In contrast, synaptic adaptations occurred at a slower timescale (~2 d) and involved decreases in miniature EPSC amplitude. To examine how these temporally distinct homeostatic responses influenced hippocampal network activity, we quantified the rate of spontaneous spiking measured by multielectrode arrays at extended timescales. M-Channel blockade triggered slow homeostatic renormalization of the mean firing rate (MFR), concomitantly accompanied by a slow synaptic adaptation. Thus, the fast intrinsic adaptation of excitatory neurons is not sufficient to account for the homeostatic normalization of the MFR. In striking contrast, homeostatic adaptations of intrinsic excitability and spontaneous MFR failed in hippocampal GABAergic inhibitory neurons, which remained hyperexcitable following chronic M-channel blockage. Our results indicate that a single perturbation such as M-channel inhibition triggers multiple homeostatic mechanisms that operate at different timescales to maintain network mean firing rate.

SIGNIFICANCE STATEMENT Persistent alterations in synaptic input elicit homeostatic plastic changes in neuronal activity. Here we show that chronic neuronal hyperexcitability, induced by M-type potassium channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in hippocampal excitatory neurons. The data indicate that the fast adaptation of intrinsic excitability depends on ongoing spiking activity but is not sufficient to provide homeostasis of the mean firing rate. Our results show that a single perturbation such as M-channel inhibition can trigger multiple homeostatic processes that operate at different timescales to maintain network mean firing rate.

FAO and its partners have launched an initiative aimed at cutting food waste across the Asia-Pacific region. Save Food Asia-Pacific Campaign targets losses both straight after harvest and between the market and people’s plates. FAO estimates that reducing global food waste by just one quarter would be sufficient to feed the 870 million people suffering from chronic hunger in the world. [...]

New research details the first forensic investigation of the Sylt concentration camp, located on the Channel Island of Alderney, since the end of WWII

Due to COVID-19, Art + Action's "Come to Your Census" project has pivoted from posters and events to social media and online outreach

He was talented and prosperous, but the young visionary worried the art world had left him behind. Then he discovered soup

Yukon officials say the territory's campgrounds will open to campers on June 4, but the territory's borders will remain closed. They also issued guidelines for some health care services to reopen.

A doctor on Manitoulin Island is encouraging seasonal residents to stay home and not to come visit during the COVID-19 pandemic.

Jamal Campbell was never quite sure how the box of food ended up at his home while growing up in the community of Jane and Finch in Toronto, but he understood what it meant to his family.

Hate crimes against Vancouver's Asian communities have increased since the early days of the outbreak and the #Elimin8hate campaign is an effort to combat that and comfort victims.

Scuffles broke out at Hong Kong's legislature Friday, with security guards ejecting several pro-democracy lawmakers, including one who was carried out by medics on a stretcher after he was injured.

OM Hungary team members put on a special Christmas programme a local refugee camp.

OM Ukraine's sports team equips and trains churches in using non-traditional sports in their summer camps.

After having some difficulty with the campers and teen leaders, OMer Stephen explains the significance of the cross and following Jesus—many respond positively.

During the summer months, OM Ukraine in Odessa facilitated a camp, during which the Lord touched the hearts of many children.

It was the highest catwalk show on earth, 300 metres above Everest Base Camp - and the Herald was the only paper in Britain to have a front row seat.

Following the University-wide commencement ceremony on May 9, Penn State Shenango will host a virtual celebration for the Class of 2020.

It was set up by tourism leaders to create an authentic picture of Scotland during the coronavirus lockdown by opening a window to people’s experiences while they stay at home.

In the aftermath of this spring's teacher protests, more educators are running for state office—and the National Education Association is seizing on the political moment.

When public schools accept an offer to move into a new building on corporate land, they open the door to interference on curriculum and faculty hiring.

An exchange between two of the top-tier candidates for president highlighted how segregation in education could prove to be a potent issue in the Democratic Party's 2020 primary.

40 groups will band together to push principles for "modernizing and elevating" teaching, but many of the groups have contrasting agendas.

Penn State Schuylkill senior Abigayle Kaiser has embraced leadership roles on campus throughout her undergraduate experience. From Schuylkill Benefitting THON, to the Lion Ambassadors, the Blue & White Society and so much more, Kaiser is a student who did it all. As she nears graduation with a full-time marketing job secured, Kaiser reflects on her time as a Penn Stater.

The swirl of attention around Democratic presidential candidate Elizabeth Warren’s story of being forced out of a teaching job when she was pregnant intensifies the spotlight on her background and K-12 credentials.

Prone sleep, bed-sharing, maternal smoking during pregnancy, and prematurity increase the risk of sudden infant death syndrome. The sudden infant death syndrome rate initially declined dramatically after the initiation of the US Back-to-Sleep campaign in 1994, but subsequently plateaued.

The risk profile has changed since the Back-to-Sleep campaign; the prevalence of simultaneous risks has remained consistent. Intrinsic and extrinsic risks provide unification into 1 underlying triple-risk model and insights into potential underlying mechanisms. (Read the full article)

With Pennsylvania Gov. Tom Wolf’s March 25 “Stay at Home” order, Penn State is updating the status of its Abington, Brandywine and Great Valley campuses.

The Newseum in Washington has just launched Decision 2012: Exploring Elections and the Media, an online resource for teaching about the presidential campaign and election.

For more than a year and a half, UN peacekeepers have continuously supported military operations conducted by the Congolese armed forces (FARDC) against the Rwandan rebels of the Democratic Forces for the Liberation of Rwanda (FDLR) in North and South Kivu.

Bacteria of the genus Campylobacter are major foodborne pathogens which have become increasingly resistant to clinically important antimicrobial agents (1)....

Florfenicol belongs to a class of phenicol antimicrobials widely used as feed additives and for the treatment of respiratory infections. In recent years, increasing resistance to florfenicol has been reported in Campylobacter spp., the leading foodborne enteric pathogen causing diarrheal diseases worldwide. Here, we reported the identification of fexA, a novel mobile florfenicol resistance gene in Campylobacter. Of the 100 Campylobacter jejuni strains isolated from poultry in Zhejiang, China, nine of them were shown to be fexA positive, and their whole genome sequences were further determined by integration of Illumina short-read and MinION long-read sequencing. The fexA gene was found in the plasmid of one strain and chromosomes of eight strains, and its location was verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Based on comparative analysis, the fexA gene was located within a region with the tet(L)-fexA-catA-tet(O) gene arrangement, demonstrated to be successfully transferrable among C. jejuni strains. Functional cloning indicated that acquisition of the single fexA gene significantly increased resistance to florfenicol, whereas its inactivation resulted in increased susceptibility to florfenicol in Campylobacter. Taken together, these results indicated that the emerging fexA resistance is horizontally transferable, which might greatly facilitate the adaptation of Campylobacter in food producing environments where florfenicols are frequently used.

Campaign Monitor is a satisfactory marketing tool, especially with email marketing features and analytics, but it trails the competition in areas like direct online support.

Penn Staters across the Commonwealth are embodying the “We Are” spirit by keeping campus food pantries open and shelves stocked to continue to serve students in need during the coronavirus pandemic.

Hazleton native Megan Bobish has joined the Penn State Hazleton Athletics Department as the newest member of its team.

Penn State Hazleton’s Student Services and Engagement team is continuing to forge personal connections with students while operating under the restrictions in the virtual environment created by the COVID-19 crisis.