WT Newsome
Jun 1, 1988; 8:2201-2211
Articles

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

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

KH Britten
Dec 1, 1992; 12:4745-4765
Articles

Acoustic overexposure, such as listening to loud music too often, results in noise-induced hearing loss. The pathologies of this prevalent sensory disorder begin within the ear at synapses of the primary auditory receptors, their postsynaptic partners and their supporting cells. The extent of noise-induced damage, however, is determined by overstimulation of primary auditory receptors, upstream of where the pathologies manifest. A systematic characterization of the electrophysiological function of the upstream primary auditory receptors is warranted to understand how noise exposure impacts on downstream targets, where the pathologies of hearing loss begin. Here, we used the experimentally-accessible locust ear (male, Schistocerca gregaria) to characterize a decrease in the auditory receptor's ability to respond to sound after noise exposure. Surprisingly, after noise exposure, the electrophysiological properties of the auditory receptors remain unchanged, despite a decrease in the ability to transduce sound. This auditory deficit stems from changes in a specialized receptor lymph that bathes the auditory receptors, revealing striking parallels with the mammalian auditory system.

SIGNIFICANCE STATEMENT Noise exposure is the largest preventable cause of hearing loss. It is the auditory receptors that bear the initial brunt of excessive acoustic stimulation, because they must convert excessive sound-induced movements into electrical signals, but remain functional afterward. Here we use the accessible ear of an invertebrate to, for the first time in any animal, characterize changes in auditory receptors after noise overexposure. We find that their decreased ability to transduce sound into electrical signals is, most probably, due to changes in supporting (scolopale) cells that maintain the ionic composition of the ear. An emerging doctrine in hearing research is that vertebrate primary auditory receptors are surprisingly robust, something that we show rings true for invertebrate ears too.

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.

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression or energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in developing and adult POMC neurons. Our studies establish a previously unrecognized role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis.

Microglial cells are considered as sensors of brain pathology by detecting any sign of brain lesions, infections, or dysfunction and can influence the onset and progression of neurological diseases. They are capable of sensing their neuronal environment via many different signaling molecules, such as neurotransmitters, neurohormones and neuropeptides. The neuropeptide VGF has been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide and has been shown to signal via C3aR1 and C1qBP receptors. The effect of TLQP21 on microglial functions in health or disease is not known. Studying microglial cells in acute brain slices, we found that TLQP21 impaired metabotropic purinergic signaling. Specifically, it attenuated the ATP-induced activation of a K⁺ conductance, the UDP-stimulated phagocytic activity, and the ATP-dependent laser lesion-induced process outgrowth. These impairments were reversed by blocking C1qBP, but not C3aR1 receptors. While microglia in brain slices from male mice lack C3aR1 receptors, both receptors are expressed in primary cultured microglia. In addition to the negative impact on purinergic signaling, we found stimulating effects of TLQP21 in cultured microglia, which were mediated by C3aR1 receptors: it directly evoked membrane currents, stimulated basal phagocytic activity, evoked intracellular Ca²⁺ transient elevations, and served as a chemotactic signal. We conclude that TLQP21 has differential effects on microglia depending on C3aR1 activation or C1qBP-dependent attenuation of purinergic signaling. Thus, TLQP21 can modulate the functional phenotype of microglia, which may have an impact on their function in health and disease.

SIGNIFICANCE STATEMENT The neuropeptide VGF and its peptides have been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide that activates C1qBP receptors, which are expressed by microglia. We show here, for the first time, that TLQP21 impairs P2Y-mediated purinergic signaling and related functions. These include modulation of phagocytic activity and responses to injury. As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated mechanism might regulate microglial activity in health and disease. We furthermore show that, in addition to C1qBP, functional C3aR1 responses contribute to TLQP21 action on microglia. However, C3aR1 responses were only present in primary cultures but not in situ, suggesting that the expression of these receptors might vary between different microglial activation states.

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.

Theoretical models and experimental evidence have suggested that connections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this study, selective lesions in the DG were made using colchicine in male Long–Evans rats, and single units from the CA3 were recorded as the rats performed visual scene memory tasks. The original scenes used in training were altered during testing by blurring to varying degrees or by using visual masks, resulting in maximal recruitment of the DG–CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. In addition, the firing rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when ambiguous scenes were presented, largely because DG-deprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also during retrieval when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.

SIGNIFICANCE STATEMENT Despite the behavioral evidence supporting the role of the dentate gyrus in pattern separation in the hippocampus, the underlying neural mechanisms are largely unknown. By recording single units from the CA3 in DG-lesioned rats performing a visual scene memory task, we report that the scene-related modulation of neural firing was significantly reduced in the DG-lesion rats compared with controls, especially when the original scene stimuli were ambiguously altered. Our findings suggest that the dentate gyrus plays an essential role during memory retrieval and performs a critical computation to make categorical rate modulation occur in the CA3 between different scenes, especially when ambiguity is present in the environment.

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. [...]

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

The head of a Sudbury-based book publishing company says she’s shifting launches online due to COVID-19.

The following is a guest post by Martha H. Kennedy, Curator of Popular & Applied Graphic Art, Prints & Photographs Division. During Will Eisner Week, March 1-7, 2020, the Library of Congress joins art schools, libraries, universities, and museums in a global celebration of this legendary creator’s contributions to the world of comic art and […]

BIS Bulletin No 8, April 2020. Information on local labour markets and Google searches can be used to construct a measure of the vulnerability of employment in different regions of the United States to the Covid-19 shock. Regional exposure to Covid-19 varies significantly, ranging from a low of 2% to a high of 98% of total local employment. We test for the usefulness of the Covid-19 exposure measure by showing that areas with higher exposure report more Google search queries related to the pandemic and unemployment benefits.

BCBS Press release "Basel Committee sets out additional measures to alleviate the impact of Covid-19", 3 April 2020

Eight COVID-19 cases are now connected to that workplace, including six employees.

"Recovery is not for the faint-hearted," says recovering addict Jeremy Raven. And sometimes, something as simple as a kind word may be the hand up that someone who is struggling needs, he says.

The Flint Registry is holding in-person enrollment across the city of Flint all week. Officials are trying to track the health of residents made ill by the Flint Water Crisis.

You may not like who you’re about to become.

The CFL and CFL Players' Association have halted discussions on potential contingency plans for the 2020 campaign due to the COVID-19 pandemic.

Mayor Jane Castor has issued a letter of apology after Tampa didn't exactly give the best of welcomes to one of its newest and most famous residents when NFL superstar Tom Brady was ejected from a downtown park while working out.

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.

Hope for a 2020 Grey Cup in Regina is slowly dwindling as the CFL hints at a season cancellation. 

Toronto’s islands are closed to the public to prevent the spread of COVID-19 and there’s no word on when tourists can return. Ali Chiasson looks at the impact the pandemic will have on the islands.

Municipalities across the province are re-evaluating their financial situations as COVID-19 continues to keep municipal facilities closed and has put other revenue streams on hold. 

Central Bank of Chile Working Papers by Carlos Madeira

The 2020 "Expanding Empathy" lecture series has moved online and added a lecture on "The Altruistic Brain," as well as a panel discussion on empathy in the time of COVID-19, both to be held on April 29 via Zoom.

Wink customers will soon have to pay a monthly subscription fee to access any of the smart home hardware that they have purchased.

Before Monday's 13-inch MacBook Pro update, the choice between the 2019 model and the 2020 MacBook Air was very clear. It is less clear today -- but we can help.

An OM couple serving in Bar, Montenegro share how a short-term team building a shelter has had positive and lasting impact on a community they serve through a club for kids.

SOLIDWORKS Image Quality settings have the biggest impact on file size and system performance. We always assumed that it would have an impact on overall performance also. The effect varies widely across different files, so we decided to do SOLIDWORKS

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One major goal of integrative and comparative biology is to understand and explain the interaction between the performance and behavior of animals in their natural environment. The Caviomorph, Octodon degu, is a native rodent species from Chile, and represents a unique model to study physiological and behavioral traits, including cognitive and sensory abilities. Degus live in colonies and have a well-structured social organization, with a mostly diurnal–crepuscular circadian activity pattern. More notable is the fact that in captivity, they reproduce and live between 5 and 7 yr and show hallmarks of neurodegenerative diseases (including Alzheimer's disease), diabetes, and cancer.

On 12 May, 130 people in Atlanta, Georgia, participate in a hike at to benefit trafficked and exploited women across our world.

OM attempts to bring Christ’s love to the darkest corners of Sham Shui Po, and to walk with those neglected by society.

Progreso, Mexico :: Reflections on the impact among churches and on people stirred up for mission, after Logos Hope's four months in Mexico.

Participants from all over the world joined together in Ireland for two weeks of training and outreach in partnership with local churches.

On 19 March, OM Australia moved into their new home, a place that will help mobilise more people and finances into missions.

A 29 year old recounts how his family fled the war zone and came to stay at OM Odessa centre

God uses theatrical evangelism camps to impact children from vulnerable populations as well as the short-term volunteers who serve.

A group of 80 teenagers from Chicago, US, bless the local community in Volcán, Panama.

Balboa, Panama :: Logos Hope's volunteers make an uplifting visit to a shelter for migrant men, testing their eyesight and handing out reading glasses.

Within just a few weeks, the corona crisis has led to a collapse of over 90 percent of flight operations in the capital region. In light of this dramatic situation, the Flughafen Berlin Brandenburg GmbH (FBB) Executive Board concluded a works agreement ...

Berlin’s airports are recording a drastic slump in passenger numbers. In March, a decline in passengers of 64.7 percent was recorded at Tegel and Schönefeld for the whole month. However, the number of passengers has continued to fall significantly over ...

Members of OM Costa Rica help a 90-year-old woman get to her doctor appointment at a hospital six hours away from her home.

Over 180 people of all ages unite in Costa Rica for the annual international outreach of OM Central America.