Spatial orientation memory plays a crucial role in animal navigation. Recent studies of tethered Drosophila melanogaster (fruit fly) in a virtual reality setting showed that the head direction is encoded in the form of an activity bump, i.e. localized neural activity, in the torus-shaped ellipsoid body (EB). However, how this system is involved in orientation working memory is not well understood. We investigated this question using free moving flies ( Drosophila melanogaster ) in a spatial orientation memory task by manipulating two EB subsystems, C and P circuits, which are hypothesized for stabilizing and updating the activity bump, respectively. To this end, we suppressed or activated two types of inhibitory ring neurons (EIP and P) which innervate EB, and we discovered that manipulating the two inhibitory neuron types produced distinct behavioral deficits, suggesting specific roles of the inhibitory neurons in coordinating the stabilization and updating functions of the EB circuits. We further elucida...

In postdiction, the last stimulus of a sequence changes the perception of the preceding stimuli. Postdiction has been reported in all sensory modalities but its neural underpinnings remain poorly understood. In the rabbit illusion, a sequence of non-equidistant stimuli presented isochronously is perceived as equidistantly spaced. This illusion might be driven by an internal prior favoring a constant-speed motion. Here, we hypothesized that pre-stimulus alpha oscillations (8 – 12 Hz), known to correlate with perceptual expectations and biases, would reflect the degree to which perceptual reports are influenced by a constant-speed prior. Human participants were presented with ambiguous visual sequences while being recorded simultaneously with MEG and EEG: the same sequences yielded an illusory perception in about half the trials, allowing contrasting brain responses elicited by identical sequences causing distinct percepts. As a proxy of an individual’s prior, we used the percentage of perceived illusion and...

GABAergic somatodendritic inhibition in the preBötzinger Complex (preBötC), a medullary site for the generation of inspiratory rhythm, is involved in respiratory rhythmogenesis and patterning. Nevertheless, whether GABA acts distally on presynaptic terminals, evoking presynaptic inhibition is unknown. Here, we begin to address this problem by measuring presynaptic Ca2+ transients in preBötC neurons, under rhythmic and non-rhythmic conditions, with two variants of genetically encoded Ca2+ indicators. Organotypic slice cultures from newborn mice, containing the preBötC, were drop-transduced with jGCaMP7s, or injected with jGCaMP7f - labeling commissural preBötC neurons. Then, Ca2+-imaging combined with whole-cell patch-clamp or field-stimulation was obtained from inspiratory preBötC neurons. We found that rhythmically active neurons expressed synchronized Ca2+ transients in soma, proximal and distal dendritic regions, and punctate synapse-like structures. Expansion microscopy revealed morphological character...

While humans and other mammals exhibit adaptation to odorants, the neural mechanisms and brain locations involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted to the brain. An alternative possibility is that adaptation occurs because of processing in the brain. We made an initial test of these possibilities using a two-color imaging strategy to simultaneously measure the activity of the olfactory receptor nerve terminals (input to the bulb) and mitral/tufted cell apical dendrites (output from the bulb) in anesthetized and awake mice. Repeated odor stimulation at the same concentration resulted in a decline in the bulb output, while the input remained relatively stable. Thus, the mammalian olfactory bulb appears to participate in generating the perception...

Neuronal proton-gated Acid-Sensing Ion Channels (ASICs) participate in the detection of tissue acidosis, a phenomenon often encountered in painful pathological diseases. Such conditions often involve in parallel the activation of various signaling pathways such as the Mitogen Activated Protein Kinases (MAPKs) that ultimately leads to phenotype modifications of sensory neurons. Here, we identify one member of the MAPKs, c-Jun N-terminal Kinase (JNK), as a new post-translational positive regulator of ASIC channels in rodent sensory neurons. Recombinant H+-induced ASIC currents in HEK293 cells are potently inhibited within minutes by the JNK inhibitor SP600125 in a subunit dependent manner, targeting both rodent and human ASIC1b and ASIC3 subunits (except mouse ASIC3). The regulation by JNK of recombinant ASIC1b- and ASIC3-containing channels (homomers and heteromers) is lost upon mutation of a putative phosphorylation site within the intracellular N- and the C-terminal domain of the ASIC1b and ASIC3 subunit,...

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive motor neuron death, where patients usually die within five 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 behavioural 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 endpoint of mSOD1G93A mice; however, our histological analysis shows that C-bouton silencing significantly improves fast twitch muscle inne...

Microglia maintain brain health and play important roles in disease and injury. Despite their known ability to proliferate, the precise nature of the population(s) capable of generating new microglia in the adult brain remains controversial. We identified Prominin-1 (CD133 or Prom1) as a putative cell surface marker of committed brain myeloid progenitor cells. We demonstrate that Prom1 expressing cells isolated from mixed cortical cultures will generate new microglia in vitro . To determine whether Prom1 expressing cells generate new microglia in vivo , we used tamoxifen inducible fate mapping in male and female mice. Induction of Cre recombinase activity at 10 weeks in Prom1 expressing cells lead to the expression of TdTomato in all Prom1 expressing progenitors and newly generated daughter cells. We observed a population of new TdTomato expressing microglia at six months of age that increased in size at nine months. When microglia proliferation was induced using a transient ischemia/reperfusion paradigm, ...

Feature-based visual attention refers to preferential selection and processing of visual stimuli based on their non-spatial attributes such as color or shape. Recent studies have highlighted the inferior frontal junction (IFJ) as a control region for feature but not spatial attention. However, the extent to which IFJ contributes to spatial versus feature attention control remains a topic of debate. We investigated in humans of both sexes the role of IFJ in the control of feature versus spatial attention in a cued visual spatial (attend-left or attend-right) and feature (attend-red or attend-green) attention task using fMRI. Analyzing cue-related fMRI using both univariate activation and multivoxel pattern analysis (MVPA), we found the following results in IFJ. First, in line with some prior studies, the univariate activations were not different for feature and spatial attentional control. Second, in contrast, the MVPA decoding accuracy was above chance level for feature attention (attend-red vs. attend-gre...

Attributing outcomes to your own actions or to external causes is essential for appropriately learning which actions lead to reward and which actions do not. Our previous work showed that this type of credit assignment is best explained by a Bayesian reinforcement learning model which posits that beliefs about the causal structure of the environment modulate reward prediction errors (RPEs) during action value updating. In this study, we investigated the brain networks underlying reinforcement learning that are influenced by causal beliefs using functional magnetic resonance imaging while human participants ( n = 31; 13 males, 18 females) completed a behavioral task that manipulated beliefs about causal structure. We found evidence that RPEs modulated by causal beliefs are represented in dorsal striatum, while standard (unmodulated) RPEs are represented in ventral striatum. Further analyses revealed that beliefs about causal structure are represented in anterior insula and inferior frontal gyrus. Finally, s...