BK channel dysfunction disrupts attention-controlled behaviors and altered perseverative responses in murine instrumental learning.

This study examined the effect of knockout of KCNMA1 gene, coding for the BK channel, on cognitive and attentional functions in mice, with an aim to better understand its implications for human neurodevelopmental disorders. The study used the 3-choice serial reaction time task (3-CSRTT) to assess the learning performance, attentional abilities, and repetitive behaviors in mice lacking the KCNMA1 gene (KCNMA1-/-) compared to wild-type (WT) controls. Results showed no significant differences in learning accuracy between the two groups. However, KCNMA1-/- mice were more prone to omitting responses to stimuli. In addition, when the timing of cue presentation was randomized, the KCNMA1-/- showed premature responses. Notably, these mice also demonstrated a marked reduction in perseverative responses, which include repeated nose-poke behaviors following decisions. These findings highlight the involvement of the KCNMA1 gene in managing attention, impulsivity, and potentially moderating repetitive actions.

Measuring Task-Related Brain Activity With Event-Related Potentials in Dynamic Task Scenario With Immersive Virtual Reality Environment.

Measurement of event-related potentials (ERPs) in simulated and real environments is advantageous for understanding cognition and behavior during practice of goal-directed activities. Recently, instead of using task-irrelevant "probe stimuli" to elicit ERPs, extraction of ERPs directly from events that occur in simulated and real environments has drawn increased attention. Among the previous ERP studies using immersive virtual reality, only a few cases elicited ERPs from task-related events in dynamic task settings. Furthermore, as far as we surveyed, there were no studies that examined the source of ERPs or correlation between ERPs and behavioral performance in 360-degree immersive virtual reality using head-mounted display. In this study, EEG signals were recorded from 16 participants while they were playing the first-person shooter game with immersive virtual reality environment. Error related negativity (ERN) and correct-(response)-related negativity (CRN) elicited by shooting-related events were successfully extracted. We found the ERN amplitudes to be correlated with the individual shooting performance. Interestingly, the main source of the ERN was the rostral anterior cingulate cortex (ACC), which is different from previous studies where the signal source was often estimated to be the more caudal part of ACC. The obtained results are expected to contribute to the evaluation of cognitive functions and behavioral performance by ERPs in a simulated environment.

The asymmetric learning rates of murine exploratory behavior in sparse reward environments.

Goal-oriented behaviors of animals can be modeled by reinforcement learning algorithms. Such algorithms predict future outcomes of selected actions utilizing action values and updating those values in response to the positive and negative outcomes. In many models of animal behavior, the action values are updated symmetrically based on a common learning rate, that is, in the same way for both positive and negative outcomes. However, animals in environments with scarce rewards may have uneven learning rates. To investigate the asymmetry in learning rates in reward and non-reward, we analyzed the exploration behavior of mice in five-armed bandit tasks using a Q-learning model with differential learning rates for positive and negative outcomes. The positive learning rate was significantly higher in a scarce reward environment than in a rich reward environment, and conversely, the negative learning rate was significantly lower in the scarce environment. The positive to negative learning rate ratio was about 10 in the scarce environment and about 2 in the rich environment. This result suggests that when the reward probability was low, the mice tend to ignore failures and exploit the rare rewards. Computational modeling analysis revealed that the increased learning rates ratio could cause an overestimation of and perseveration on rare-rewarding events, increasing total reward acquisition in the scarce environment but disadvantaging impartial exploration.

Highly reliable, targeted photothermal cancer therapy combined with thermal dosimetry using a near-infrared absorbent.

Photothermal therapy (PTT) using a photo-absorbent in the near-infrared (NIR) region is an effective methodology for local cancer treatment. Before PTT using a NIR absorbent is executed, the operator generally determines the two parameters of fluence rate and irradiation time. However, even if the irradiation parameters are unchanged, the therapeutic effect of PTT is often different for individual tumors. Hence, we examined the therapeutic effect of PTT using a NIR absorbent (ICG lactosome) while changing two parameters (fluence rate and irradiation time) in various combinations. As a result, there was no robust correlation between those parameters and the therapeutic effect. Compared to those parameters, we found that a more reliable determinant was maintenance of the tumor temperature above 43 °C during NIR irradiation. To reconfirm the significance of the determinant, we developed a new system that can regulate the temperature at the NIR irradiation site at a constant level. By using the new system, we verified the treatment outcomes for tumors in which the NIR absorbent had accumulated. All of the tumors that had been kept at 43 °C during NIR irradiation were cured, while none of the tumors that had been kept at a temperature below 41 °C were cured. In conclusion, PTT using a NIR absorbent with thermal dosimetry is a highly reliable treatment for cancer.

Inkjet-Printed Neural Electrodes with Mechanically Gradient Structure.

Flexible materials are important for the development of neural probes in recording stable signals (spikes) in vivo. Here, we present inkjet-printed, flexible neural probes for spike recording by using polymeric thin films. The neural probes were constructed from 400 nm-thick poly(d,l-lactic acid) nanofilms, inkjet-printed lines consisting of Au and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate nanoinks, and fluoropolymer layers. Microelectrodes were exposed by cutting the edge with a razor. The 6 µm-thick probes were connected to the external amplifiers by gradual increase of stiffness with thickness-dependent manner. The probe was formed into a needle shape, which recorded spikes from mouse thalamus in vivo.

Adrenergic receptor-mediated modulation of striatal firing patterns.

Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The ß-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α1-AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the ß-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. ß-ARs and α1-ARs work in opposition controlling the striatal firing initiation and the firing increment.