Theories have proposed that, in sensory cortices, learning can enhance top-down modulation by higher brain areas while reducing bottom-up sensory drives. To address circuit mechanisms underlying this ...process, we examined the activity of layer 2/3 (L2/3) excitatory neurons in the mouse primary visual cortex (V1) as well as L4 excitatory neurons, the main bottom-up source, and long-range top-down projections from the retrosplenial cortex (RSC) during associative learning over days using chronic two-photon calcium imaging. During learning, L4 responses gradually weakened, whereas RSC inputs became stronger. Furthermore, L2/3 acquired a ramp-up response temporal profile, potentially encoding the timing of the associated event, which coincided with a similar change in RSC inputs. Learning also reduced the activity of somatostatin-expressing inhibitory neurons (SOM-INs) in V1 that could potentially gate top-down inputs. Finally, RSC inactivation or SOM-IN activation was sufficient to partially reverse the learning-induced changes in L2/3. Together, these results reveal a learning-dependent dynamic shift in the balance between bottom-up and top-down information streams and uncover a role of SOM-INs in controlling this process.
•Recruitment of top-down control is proposed as a unified principle of cortical learning.•Microscopic circuit dissection revealed dynamic recruitment of top-down activity during sensory ...learning.•Macroscopic activity analysis uncovered top-down-mediated orchestration of cortical activity during motor learning.
Cognitive control of the brain flexibly maps incoming sensory information onto execution of actions appropriate for the current goal. Learning is a process that enables the brain to estimate current states of the world by extracting its spatiotemporal structure and generate goal-directed motor outputs through selective association of events or movement refinement. Accumulating evidence suggests that top-down control from higher-order brain areas modulates downstream neural activity and changes local computations that are critical for the execution of learned behavior. Recent technological advances in multi-site recordings and optogenetic approaches are beginning to reveal more direct evidence of top-down cognitive control by monitoring and perturbing activity of top-down inputs and observing its causal consequences on behavior and downstream neural dynamics. Here I highlight that learning-related changes in neural circuits in distinct domains of learning converge onto a unified principle; namely recruitment of top-down control whether it involves sensory, motor or offline learning. Recruitment of top-down control may reflect experience-dependent adaptation and integration of internal models for refined state estimation and goal-directed optimal behavior.
Synapses in the brain are continuously modified by experience, but the mechanisms are poorly understood. In vitro and theoretical studies suggest threshold-lowering interactions between nearby ...synapses that favor clustering of synaptic plasticity within a dendritic branch. Here, a fluorescently tagged AMPA receptor-based optical approach was developed permitting detection of single-synapse plasticity in mouse cortex. Sensory experience preferentially produced synaptic potentiation onto nearby dendritic synapses. Such clustering was significantly reduced by expression of a phospho-mutant AMPA receptor that is insensitive to threshold-lowering modulation for plasticity-driven synaptic incorporation. In contrast to experience, sensory deprivation caused homeostatic synaptic enhancement globally on dendrites. Clustered synaptic potentiation produced by experience could bind behaviorally relevant information onto dendritic subcompartments; global synaptic upscaling by deprivation could equally sensitize all dendritic regions for future synaptic input.
► Recent history of in vivo synaptic plasticity is identified at individual spines ► Sensory experience drives compartmentalized synaptic potentiation ► Sensory deprivation drives global synaptic upscaling ► Plasticity threshold controls compartmentalized synaptic potentiation
The relationship between the brain and the environment is flexible, forming the foundation for our ability to learn. Here we review the current state of our understanding of the modifications in the ...sensorimotor pathway related to sensorimotor learning. We divide the process into three hierarchical levels with distinct goals: (1) sensory perceptual learning, (2) sensorimotor associative learning, and (3) motor skill learning. Perceptual learning optimizes the representations of important sensory stimuli. Associative learning and the initial phase of motor skill learning are ensured by feedback-based mechanisms that permit trial-and-error learning. The later phase of motor skill learning may primarily involve feedback-independent mechanisms operating under the classic Hebbian rule. With these changes under distinct constraints and mechanisms, sensorimotor learning establishes dedicated circuitry for the reproduction of stereotyped neural activity patterns and behavior.
Makino et al. review the current understanding of neural mechanisms underlying sensorimotor learning, focusing on three hierarchical levels of simultaneously occurring neural changes and highlighting the distinct goals, constraints, and their solutions at each level.
Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity ...of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements.
•Longitudinal wide-field calcium imaging of cortex during motor learning•Motor learning compressed and stabilized sequential activity across cortex•Motor learning altered the information flow across cortex•Premotor cortex acquired a leading role with motor learning
With longitudinal wide-field calcium imaging, Makino et al. uncover novel principles underlying transformations of learning-related macroscopic dynamics, where motor learning leads to temporally compressed and more reliable sequential activation of cortical modules, with premotor cortex orchestrating the cortical activity.
Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding ...factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome.
The gastrointestinal tract is believed to be colonized rapidly with bacteria immediately from birth. The source of these intestinal microbes is an ongoing topic of interest because increasing ...evidence suggests that the composition of the initial intestinal bacterial colonization strongly affects health. In particular, the source of bifidobacteria has received marked attention because these bacteria are suggested to play a crucial role in protecting against susceptibility to diverse diseases later in life. However, the source of these microbes has remained unclear. Recently, it was confirmed that mothers transmit their unique bifidobacterial strains to their children shortly after birth. The transmitted strains predominate during early infancy, suggesting that maternal intestinal bifidobacteria are an important source of the infant gut microbiota. Accordingly, maintenance of a healthy, balanced gut microbiota during pregnancy has an important positive influence on the newborn gut microbiota.
The newly synthesized Keio Fluors, which are based on boron-dipyrromethene (BDP), have excellent and useful optical properties: vivid colors and sharp emission in the visible−near-infrared region ...(583−738 nm), high quantum yields (Φ: 0.56−0.98), high extinction coefficients (185000−288000 M-1 cm-1), and good photostabilities. These optical properties are superior to many of the existing fluorescent dyes such as rhodamines, cyanines, or other BDP-based fluorescent dyes.
Background: Most surveillance programs for postoperative infection focus on surgical site infections (SSI). However, postoperative remote infections are of emerging clinical importance. Using data ...from a multicenter survey administered to patients who underwent gastrointestinal surgery, we investigated the incidence of SSI and remote infection after colorectal surgery. Methods: From September 2015 through March 2016, 1,724 patients underwent colorectal surgery in 28 affiliated centers in Japan. We retrospectively recorded patient age, sex, surgical site, surgical approach, wound classification, performance status at discharge, and postoperative infection status. Results: Postoperative infection was noted in 236 (13.7%) patients; 150 and 86 patients underwent colon and rectal surgeries, respectively (incidence of postoperative infection: 13.7% and 14.8%). The incidence of postoperative infection was significantly lower after laparoscopic surgery than after open surgery, in colon and rectal surgery (p < 0.001). Among patients with postoperative infections, 211 (89.4%) had a single infection and 25 (10.6%) had multiple infections. Among patients with a single postoperative infection, SSI and remote infection occurred in 143 (60.6%) and 68 (28.8%) patients, respectively. The most common multiple postoperative infections were "incisional and organ/space SSIs" and "organ/space SSI and bacteremia of unknown origin" (n = 3 each). Conclusions: This study revealed the prevalence distributions for postoperative SSI and remote infections. Because of the substantial effect of remote infections on patient quality of life and the associated social burden, prospective periodic surveillance for SSI and remote infection is necessary for careful evaluation and prevention.
Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent ...anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate early gene products, c-fos and Zif268, as indicators of recently activated neurons, we show that previous exposure to an enriched environment increases the total number of new neurons and the number of new neurons responding to reexposure to the same environment. The increase in the density of activated new neurons occurred specifically in response to exposure to the same environment but not to a different experience. Furthermore, we found that these experience-specific modifications are affected exclusively by previous exposure around the second week after neuronal birth but not later than 3 weeks. Thus, the animal's experience within a critical period during an immature stage of new neurons determines the survival and population response of the new neurons and may affect later neural representation of the experience in the dentate gyrus. This experience-specific functional modification through adult neurogenesis could be a mechanism by which new neurons exert a long-term influence on the function of the dentate gyrus related to learning and memory.
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