Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA. In contrast to the classical theory that recurrent synaptic excitation supports persistent firing, suppression of persistent firing by NA was independent of synaptic transmission, indicating that the mechanism is intrinsic to individual cells. In agreement with detrimental effects of cAMP on working memory, we demonstrate that the suppressive effect of NA was through cAMP-PKA pathway. In addition, activation of β1 and/or β3 adrenergic receptors, which increases cAMP levels, suppressed persistent firing. These results are in line with working...

Animal models suggest that interactions between the hippocampus and ventral tegmental area (VTA) underlie the onset and etiology of psychosis. While a large body of research has separately characterized alterations in hippocampal and VTA function in psychosis, alterations across the VTA and hippocampus have not been characterized in first-episode psychosis (FEP). As the phase of psychosis most proximal to conversion, studies specifically focused on FEP are valuable to psychosis research. Here, we characterize alterations in VTA-hippocampal interactions across male and female human participants experiencing their first episode of psychosis using resting state functional magnetic resonance imaging (rsfMRI). In comparison to age and sex matched healthy controls (HCs), FEP individuals had significantly greater VTA-hippocampal functional coupling but significantly less VTA-striatal functional coupling. Further, increased VTA-hippocampal functional coupling in FEP correlated with individual differences in psycho...

We previously argued that the neuroscience community has a role in environmental conservation because protection of biodiversity and the specialized behavioral adaptions of animals is essential to understanding brain structure and function. Preserving biodiversity and the natural world is also linked to human mental health and broadens our insight on the origins of psychiatric disorders like stress, anxiety, and depression. The study of neuroscience has become a global scientific pursuit that involves thousands of researchers and has an economic impact in the billions of dollars. As a group of biomedical research scientists, neuroscientists have the knowledge base and public credibility to convincingly promote sustainable environmental actions and policies. Here, we outline several key areas in which we as a neuroscience academic community can participate to preserve a rich global biodiversity and confront the environmental crises that lie before us.

The ability to discriminate spikes that encode a particular stimulus from spikes produced by background activity is essential for reliable information processing in the brain. We describe how synaptic short-term plasticity (STP) modulates the output of presynaptic populations as a function of the distribution of the spiking activity and find a strong relationship between STP features and sparseness of the population code, which could solve this problem. Furthermore, we show that feedforward excitation followed by inhibition (FF-EI), combined with target-dependent STP, promote substantial increase in the signal gain even for considerable deviations from the optimal conditions, granting robustness to this mechanism. A simulated neuron driven by a spiking FF-EI network is reliably modulated as predicted by a rate analysis and inherits the ability to differentiate sparse signals from dense background activity changes of the same magnitude, even at very low signal-to-noise conditions. We propose that the STP-ba...

Everyone agrees that we do not yet understand how brains work, neither well enough to satisfactorily explain basic functions such as memory nor to design effective interventions to restore mental health. This is one of the great scientific challenges of our era, with huge implications not only for human health but for insight into all animal life and for the development of future technologies. How should resources be invested to foster the necessary leap toward understanding? Given the pressing societal need and the very high public expectations of neuroscience, stoked by TED talks, New York Times articles, and sci fi, the pressures riding on choices of funding targets are enormous. Against this background, 2013 was a banner year for the brain: both the European Union and the United States agreed to devote unprecedented support specifically to neuroscience. The European Union funded the billion-dollar Human Brain Project (HBP; Amunts et al, 2016), whose centerpiece was a team science effort to develop neu...

This commentary puts the In Silico movie in perspective of the Human Brain Project (HBP) and clarifies major differences between this project and the Blue Brain Project, emphasizing that the two projects are very different in scope.

Highlighted Research Paper: [[The Role of Location-Context Binding in Nonspatial Visual Working Memory, by Ying Cai, Jacqueline M. Fulvio, Qing Yu, Andrew D. Sheldon, and Bradley R. Postle (2020).][2]][2] []: /lookup/doi/10.1523/ENEURO.0430-20.2020

In the article, “Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and Aminergic Modulatory Motor Terminals …

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment. We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex/parieto-occipital sulcus and anterior hippocampus did not change systematically as a function learning in older compared to younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects ...

When performing a long chain of actions in rapid sequence, future movements need to be planned concurrently with ongoing action. However, how far ahead we plan, and whether this ability improves with practice, is currently unknown. Here, we designed an experiment in which healthy volunteers produced sequences of 14 finger presses quickly and accurately on a keyboard in response to numerical stimuli. On every trial, participants were only shown a fixed number of stimuli ahead of the current keypress. The size of this viewing window varied between 1 (next digit revealed with the pressing of the current key) and 14 (full view of the sequence). Participants practiced the task for 5 days, and their performance was continuously assessed on random sequences. Our results indicate that participants used the available visual information to plan multiple actions into the future, but that the planning horizon was limited: receiving information about more than three movements ahead did not result in faster sequence pro...