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...

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements—especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day 8 (P8), nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich rep...

Constanze Krohs, Christoph Körber, Lena Ebbers, Faiza Altaf, Giulia Hollje, et al. (see pages [6796–6811][1]) MicroRNAs (miRs) fine tune protein expression by binding to and repressing translation of target mRNAs. Several miRs have important roles in nervous system development and function,

Episodic memory requires information to be stored and recalled in sequential order, and these processes are disrupted in schizophrenia. Hippocampal phase precession and theta sequences are thought to provide a biological mechanism for sequential ordering of experience at timescales suitable for plasticity. These phenomena have not previously been examined in any models of schizophrenia risk. Here, we examine these phenomena in a maternal immune activation (MIA) rodent model. We show that while individual pyramidal cells in the CA1 region continue to precess normally in MIA animals, the starting phase of precession as an animal enters a new place field is considerably more variable in MIA animals than in controls. A critical consequence of this change is a disorganization of the ordered representation of experience via theta sequences. These results provide the first evidence of a biological-level mechanism that, if it occurs in schizophrenia, may explain aspects of disorganized sequential processing that c...

In the article “Loss of TREM2 Confers Resilience to Synaptic and Cognitive Impairment in Aged Mice,” by Wenhui Qu and Ling Li, which appeared on pages [9552–9563][1] of the December 9, 2020 issue, the order of panels A and C was accidentally switched within [Figure 1][2]. The corrected figure