The term “memory strength” generally refers to how well one remembers something but more precisely it contains multiple modalities, such as how easily, how accurately, how confidently and how vividly we remember it. In human, these modalities of memory strength are dissociable. In this study, we asked whether we can isolate a behavioral component that is dissociable from others in hippocampus-dependent memory tasks in mice, which potentially reflect a modality of memory strength. Using a virus-mediated inducible method, we ablated immature neurons in the dentate gyrus in mice after we trained the mice with hippocampus-dependent memory tasks normally. In memory retrieval tests, these ablated mice initially show intact performance. However, the ablated mice ceased learned behavior prematurely within a trial compared with control mice. In addition, the ablated mice showed shorter duration of individual episodes of learned behavior. Both affected behavioral measurements point to persistence of learned behavior...

It is widely assumed that we select actions we value the most. While the influence of rewards on decision-making has been extensively studied, evidence regarding the influence of motor costs is scarce. Specifically, how and when motor costs are integrated in the decision process is unclear. Twenty-two right-handed human participants performed a reward-based target selection task by reaching with their right arm toward one of two visual targets. Targets were positioned in different directions according to biomechanical preference, such that one target was systematically associated with a lower motor cost than the other. Only one of the two targets was rewarded, either in a congruent or incongruent manner with respect to the associated motor cost. A timed-response paradigm was used to manipulate participants’ reaction times (RT). Results showed that when the rewarded target carried the highest motor cost, movements produced at short RT (<350ms) were deviated toward the other (i.e., non-rewarded, low-cost) ta...

Pitch is a perceptual attribute enabling perception of melody. There is no consensus regarding the fundamental nature of pitch and its underlying neural code. A stimulus which has received much interest in psychophysical and computational studies is noise with a sharp spectral edge. High- or low-pass noise gives rise to a pitch near the edge frequency (“monaural edge pitch”, MEP). The simplicity of this stimulus, combined with its spectral and autocorrelation properties, make it an interesting stimulus to examine spectral versus temporal cues that could underly its pitch. We recorded responses of single auditory nerve fibers in chinchilla to MEP-stimuli varying in edge frequency. Temporal cues were examined with shuffled autocorrelogram (SAC) analysis. Correspondence between the population’s dominant interspike interval and reported pitch estimates was poor. A fuller analysis of the population interspike interval distribution, which incorporates not only the dominant but all intervals, results in good matc...

Cross-sectional versus longitudinal comparisons of age-related change have often revealed differing results. In the current study, we employed within-subject task-based fMRI to investigate changes in voxel-based activations and behavioral performance across the lifespan in the Reference Ability Neural Network (RANN) cohort, at both baseline and 5-year follow-up. We analyzed fMRI data from between 127 and 159 participants (20-80 years), on a battery of tests relating to each of four cognitive reference abilities (RAs). We applied a Gaussian age kernel to capture continuous change across the lifespan using a 5-year sliding window centered on each age in our participant sample, with a subsequent division into young, middle, and old age brackets. This method was applied separately to both cross-sectional approximations of change and real longitudinal changes adopting a comparative approach. We then focused on longitudinal measurements of neural change to identify regions expressing peak changes and fluctuation...

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 (P) 8, 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 repr...

Brain microinfarcts are prevalent in humans, however due to the inherent difficulty of identifying and localizing individual microinfarcts, brain-wide quantification is impractical. In mice, microinfarcts have been created by surgically introducing microemboli into the brain, but a major limitation of this model is the absence of automated methods to identify and localize individual occlusions. We present a novel and semi-automated workflow to identify the anatomical location of fluorescent emboli (microspheres) within the mouse brain through histological processing and atlas registration. By incorporating vibratome block-face imaging with the QuickNII brain registration tool, we show that the anatomical location of microspheres can be accurately registered to brain structures within the Allen mouse brain (AMB) atlas (e.g. somatomotor areas, hippocampal region, visual areas, etc.). Compared to registering images of slide mounted sections to the AMB atlas, microsphere location was more accurately determined...

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC-BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental c...

Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the central nucleus of the amygdala (CeA) neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague-Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA but not lateral/basolateral nucleus of the amygdala (LA/BLA) abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced long-term depression (LTD) at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPARs trafficking and endocytosis from syna...

Iron is an essential co-factor for several metabolic processes, including the generation of adenosine triphosphate (ATP) in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo . Due to their close proximity to axons, Schwann cells (SCs) are a likely source of iron for axonal mitochondria in the peripheral nervous system. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that SCs express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp knockout (KO) mice, SCs accumulate iron, because Fpn requires to partner with Cp to export iron. Axons and SCs also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvie...

Mutations in the X-linked cell adhesion protein PCDH19 lead to seizures, cognitive impairment and other behavioral comorbidities when present in a mosaic pattern. Neither the molecular mechanisms underpinning this disorder, nor the function of PCDH19 itself are well understood. By combining RNA in situ hybridization with immunohistochemistry and analyzing single cell RNAseq datasets, we reveal Pcdh19 expression in cortical interneurons and provide a first account of the subtypes of neurons expressing Pcdh19 / PCDH19 , both in the mouse and the human cortex. Our quantitative analysis of the Pcdh19 mutant mouse exposes subtle changes in cortical layer composition, with no major alterations of the main axonal tracts. In addition, Pcdh19 mutant animals, particularly females, display preweaning behavioral changes, including reduced anxiety and increased exploratory behavior. Importantly, our experiments also reveal an effect of the social environment on the behavior of wild-type littermates of Pcdh19 mutant mic...