The detection of novelty indicates changes in the environment and the need to update existing representations. In response to novelty, interactions across the VTA-hippocampal circuit support experience-dependent plasticity in the hippocampus. While theories have broadly suggested plasticity-related changes are also instantiated in the cortex, research has also shown evidence for functional heterogeneity in cortical networks. It therefore remains unclear how the hippocampal-VTA circuit engages cortical networks, and whether novelty targets specific cortical regions or diffuse, large-scale cortical networks. To adjudicate the role of the VTA and hippocampus in cortical network plasticity, we used fMRI to compare resting-state functional coupling before and following exposure to novel scene images in human subjects of both sexes. Functional coupling between right anterior hippocampus and VTA was enhanced following novelty exposure. However, we also found evidence for a double dissociation, with anterior hippo...

A hallmark neuronal correlate of working memory (WM) is stimulus-selective spiking activity of neurons in prefrontal cortex (PFC) during mnemonic delays. These observations have motivated an influential computational modeling framework in which WM is supported by persistent activity. Recently this framework has been challenged by arguments that observed persistent activity may be an artifact of trial-averaging, which potentially masks high variability of delay activity at the single-trial level. In an alternative scenario, WM delay activity could be encoded in bursts of selective neuronal firing which occur intermittently across trials. However, this alternative proposal has not been tested on single-neuron spike-train data. Here, we developed a framework for addressing this issue by characterizing the trial-to-trial variability of neuronal spiking quantified by Fano factor (FF). By building a doubly stochastic Poisson spiking model, we first demonstrated that the burst-coding proposal implies a significan...

Neural response properties that typify primary sensory afferents are critical to fully appreciate because they establish and, ultimately, represent the fundamental coding design used for higher-level processing. Studies illuminating the center-surround receptive fields of retinal ganglion cells, for example, were ground-breaking because they determined the foundation of visual form detection. For the auditory system, a basic organizing principle of the spiral ganglion afferents is their extensive electrophysiological heterogeneity establishing diverse intrinsic firing properties in neurons throughout the spiral ganglion. Moreover, these neurons display an impressively large array of neurotransmitter receptor types that are responsive to efferent feedback. Thus, electrophysiological diversity and its neuromodulation is a fundamental encoding mechanism contributed by the primary afferents in the auditory system. To place these features into context we evaluated the effects of hyperpolarization and cAMP on t...

Current understanding of the neural processes underlying human grasping suggests that grasp computations involve gradients of higher- to lower-level representations and, relatedly, visual to motor processes. However, it is unclear whether these processes evolve in a strictly canonical manner from higher to intermediate, and to lower levels given that this knowledge importantly relies on functional imaging which lacks temporal resolution. To examine grasping in fine temporal detail here we used multivariate EEG analysis. We asked participants to grasp objects while controlling the time at which crucial elements of grasp programs were specified. We first specified the orientation with which participants should grasp objects and only after a delay we instructed participants about which effector(s) to use to grasp, either the right, or the left hand. We also asked participants to grasp with both hands because bimanual and left-hand grasping share intermediate level grasp representations. We observed that grasp...

Gustometers have made it possible to deliver liquids in functional magnetic resonance imaging (fMRI) settings for decades, and mouthpieces are a critical part of these taste delivery systems. Here, we propose an innovative 3D-printed fMRI mouthpiece inspired by children’s pacifiers, allowing human participants to swallow while lying down in an MRI scanner. We used a large sample to validate the effectiveness of our method. The results suggest that the mouthpiece can be used to deliver taste stimuli by showing significant clusters of activation in the insular and piriform cortex, which are regions that have been consistently identified in taste processing. This mouthpiece fulfills several criteria guaranteeing a gustatory stimulus of quality, making the delivery precise and reliable. Moreover, this new pacifier-shaped design is simple and cheap to manufacture, hygienic, comfortable to keep in the mouth, and flexible to use in diverse cases. We hope that this new method will promote and facilitate the study ...

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive motor neuron death, where patients usually die within 5 years of diagnosis. Previously, we showed that the C-boutons, which are large cholinergic synapses to motor neurons that modulate motor neuron activity, are necessary for behavioral compensation in mSOD1G93A mice, a mouse model for ALS. We reasoned that, since the C-boutons likely increase the excitability of surviving motor neurons to compensate for motor neuron loss during ALS disease progression, then amplitude modulation through the C-boutons likely increases motor neuron stress and worsens disease progression. By comparing male and female mSOD1G93A mice to mSOD1G93A mice with genetically silenced C-boutons [ mSOD1G93A ; Dbx1::cre ; ChATfl/fl ( mSOD1G93A/Coff )], we show that the C-boutons do not influence the humane end point of mSOD1G93A mice; however, our histologic analysis shows that C-bouton silencing significantly improves fast-twitch muscle inn...

Cortical oscillations have been proposed to play a functional role in speech and music perception, attentional selection, and working memory, via the mechanism of neural entrainment. One of the properties of neural entrainment that is often taken for granted is that its modulatory effect on ongoing oscillations outlasts rhythmic stimulation. We tested the existence of this phenomenon by studying cortical neural oscillations during and after presentation of melodic stimuli in a passive perception paradigm. Melodies were composed of ∼60 and ∼80 Hz tones embedded in a 2.5 Hz stream. Using intracranial and surface recordings in male and female humans, we reveal persistent oscillatory activity in the high-γ band in response to the tones throughout the cortex, well beyond auditory regions. By contrast, in response to the 2.5 Hz stream, no persistent activity in any frequency band was observed. We further show that our data are well captured by a model of damped harmonic oscillator and can be classified into thre...

Spontaneous action potential discharge (spAP) is both ubiquitous and functionally relevant during neural development. spAP remains a prominent feature of supraspinal networks in maturity, even during unconsciousness. Evidence suggests that spAP persists in mature spinal networks during wakefulness, and one function of spAP in this context could be maintenance of a “ready state” to execute behaviors. The extent to which spAP persists in mature spinal networks during unconsciousness remains unclear, and its function(s), if any, are likewise unresolved. Here, we attempt to reconcile some of the questions and contradictions that emerge from the disintegrated picture of adult spinal spAP currently available. We recorded simultaneously from large populations of spinal interneurons in vivo in male rats, characterizing the spatial distribution of spAP in the lumbar enlargement and identifying subgroups of spontaneously active neurons. We find (1) concurrent spAP throughout the dorsoventral extent of the gray matte...

Carlos Costas-Insua, Estefanía Moreno, Irene B. Maroto, Andrea Ruiz-Calvo, Raquel Bajo-Grañeras, et al. (see pages [7924–7941][1]) Endocannabinoids are produced at postsynaptic sites throughout the brain, and they act predominantly on presynaptic G-protein-coupled CB1 receptors (CB1Rs) to

The Journal of Neuroscience will celebrate Peer Review Week this year by thanking some of our most dedicated reviewers personally and acknowledging a few of them publicly. That acknowledgment of the time, effort, and commitment our peer reviewers contribute is the best part of Peer Review Week. Our