Synaptic inputs that target distal regions of neuronal dendrites can often generate local dendritic spikes that can amplify synaptic depolarization, induce synaptic plasticity, and enhance neuronal output. However, distal dendritic spikes are subject to significant attenuation by dendritic cable properties, and often produce only a weak subthreshold depolarization of the soma. Nonetheless, such spikes have been implicated in memory storage, sensory perception and place field formation. How can such a weak somatic response produce such powerful behavioral effects? Here, we use dual dendritic and somatic recordings in acute hippocampal slices of male mice to reveal that dendritic spike propagation, but not spike initiation, is strongly enhanced when the somatic resting potential is depolarized, likely as a result of increased inactivation of A-type K+ channels. Somatic depolarization also facilitates the induction of a form of dendritic spike driven heterosynaptic plasticity that enhances memory specificity....

This paper is about neural mechanisms of direction selectivity (DS) in macaque primary visual cortex, V1. We present data (on male macaque) showing strong DS in a majority of simple cells in V1 layer 4Cα, the cortical layer that receives direct afferent input from the magnocellular division of the lateral geniculate nucleus (LGN). Magnocellular LGN cells are not direction-selective. To understand the mechanisms of DS, we built a large-scale, recurrent model of spiking neurons called DSV1. Like its predecessors, DSV1 reproduces many visual response properties of V1 cells including orientation selectivity. Two important new features of DSV1 are (1) DS is initiated by small, consistent dynamic differences in the visual responses of OFF and ON Magnocellular LGN cells, and (2) DS in the responses of most model simple cells is increased over those of their feedforward inputs; this increase is achieved through dynamic interaction of feedforward and intracortical synaptic currents without the use of intracortical ...

Altruism, defined as costly other-regarding behavior, varies considerably across people and contexts. One prominent context in which people frequently must decide on how to socially act is under stress. How does stress affect altruistic decision-making and through which neurocognitive mechanisms? To address these questions, we assessed neural activity associated with charitable giving under stress. Human participants (males and females) completed a charitable donation task before and after they underwent either a psychosocial stressor or a control manipulation, while their brain activity was measured using functional magnetic resonance imaging. As the ability to infer other people's mental states (i.e., mentalizing) predicts prosocial giving and may be susceptible to stress, we examined whether stress effects on altruism depend on participants' general capacity to mentalize, as assessed in an independent task. Although our stress manipulation per se had no influence on charitable giving, increases in the s...

Response inhibition is a core executive function enabling adaptive behavior in dynamic environments. Human and animal models indicate that inhibitory control and control networks are modulated by noradrenaline, arising from the locus coeruleus. The integrity (i.e., cellular density) of the locus coeruleus noradrenergic system can be estimated from magnetization transfer (MT)-sensitive magnetic resonance imaging (MRI), in view of neuromelanin present in noradrenergic neurons of older adults. Noradrenergic psychopharmacological studies indicate noradrenergic modulation of prefrontal and frontostriatal stopping-circuits in association with behavioral change. Here, we test the noradrenergic hypothesis of inhibitory control, in healthy adults. We predicted that locus coeruleus integrity is associated with age-adjusted variance in response inhibition, mediated by changes in connectivity between frontal inhibitory control regions. In a preregistered analysis, we used MT MRI images from N = 63 healthy humans aged ...

Jacqueline M. Ehrman, Paloma Merchan-Sala, Lisa A. Ehrman, Bin Chen, Hee-Woong Lim, et al. (see pages [3344–3364][1]) Axons that extend long distances often make multiple turns as they grow along stereotyped trajectories toward their targets. Some axons seem to cheat at this task by simply

Odours are transported by turbulent air currents, creating complex temporal fluctuations in odour concentration that provide a potentially informative stimulus dimension. Recently, we have shown that mice are able to discriminate odour stimuli based on their temporal structure, indicating that information contained in the temporal structure of odour plumes can be extracted by the mouse olfactory system. Here, using in vivo extra- and intracellular electrophysiological recordings, we show that mitral and tufted cells (M/TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odour stimuli up to at least 20 Hz. A substantial population of cell-odour pairs showed significant coupling of their subthreshold membrane potential with the odour stimulus at both 2Hz (29/70) and the supra-sniff frequency 20Hz (24/70). Furthermore, M/TCs show differential coupling of their membrane potential to odour concentration fluctuations with tufted cells coupling more strongly for t...

Traumatic brain injury (TBI) is associated with an increased risk of cognitive, psychiatric, and neurodegenerative complications that may develop after injury. Increased microglial reactivity following TBI may underlie chronic neuroinflammation, neuropathology, and exaggerated responses to immune challenges. Therefore, the goal of this study was to force turnover of trauma-associated microglia that develop after diffuse TBI and determine if this alleviated chronic inflammation, improved functional recovery and attenuated reduced immune reactivity to lipopolysaccharide (LPS) challenge. Male mice received a midline fluid percussion injury and 7 days later were subjected to a forced microglia turnover paradigm using CSF1R antagonism (PLX5622). At 30 days post injury (dpi), cortical gene expression, dendritic complexity, myelin content, neuronal connectivity, cognition, and immune reactivity were assessed. Myriad neuropathology-related genes were increased 30 dpi in the cortex, and 90% of these gene changes we...

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular projections from the preoptic area of the hypothalamus (POA) to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence tha...

Cortical GABAergic interneurons have been shown to fulfil important roles by inhibiting excitatory principal neurons. Recent transcriptomic studies have confirmed seminal discoveries that used anatomical and electrophysiological methods highlighting the existence of multiple different classes of GABAergic interneurons. Although some of these studies have emphasized that inter-regional differences may exist for a given class, the extent of such differences remains unknown. To address this problem, we used single-cell Patch-RNAseq to characterise neuropeptide Y (NPY)-positive GABAergic interneurons in superficial layers of the primary auditory cortex and in distal layers of area CA3 in mice. We found that more than 300 genes are differentially expressed in NPY-positive neurons between these two brain regions. For example, the AMPA receptor auxiliary subunit Shisa9/CKAMP44 and the 5HT2a receptor are significantly higher expressed in auditory NPY-positive neurons. These findings guided us to perform pharmacolo...

Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here we investigated the effects of repeated SDS in male BALB/c mice over the subsequent 2 weeks. Some defeated mice immediately exhibited social avoidance whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into 2 groups based on the level of social avoidance, namely avoidant and non-avoidant mice. The characteristic of avoidance or non-avoidance in each individual was not fixed over the 2 weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than 2 weeks after the end of the stress exposure. Following social interac...