Distinct roles of parvalbumin- and somatostatin-expressing neurons in flexible representation of task variables in the prefrontal cortex.
- 作者列表："Jeong H","Kim D","Song M","Paik SB","Jung MW
:A hallmark of the prefrontal cortex (PFC) is flexible representation of task-relevant variables. To investigate roles of different interneuron subtypes in this process, we examined discharge characteristics and inactivation effects of parvalbumin (PV)- and somatostatin (SST)-expressing neurons in the mouse PFC during probabilistic classical conditioning. We found activity patterns and inactivation effects differed between PV and SST neurons: SST neurons conveyed cue-associated quantitative value signals until trial outcome, whereas PV neurons maintained valence signals even after trial outcome. Also, PV, but not SST, neuronal population showed opposite responses to reward and punishment. Moreover, inactivation of PV, but not SST, neurons affected outcome responses and activity reversal of pyramidal neurons. Modeling suggested opposite responses of PV neurons to reward and punishment as an efficient mechanism for facilitating rapid cue-outcome contingency learning. Our results suggest primary roles of mPFC PV neurons in rapid value updating and SST neurons in predicting values of upcoming events.
: 前额叶皮层 (PFC) 的一个标志是任务相关变量的灵活表示。为了研究不同中间神经元亚型在这一过程中的作用，我们检测了小白蛋白 (PV) 和生长抑素 (SST) 的放电特性和失活效应-在概率经典条件反射过程中表达小鼠 PFC 中的神经元。我们发现 PV 和 SST 神经元之间的活动模式和失活效应不同: SST 神经元传递线索相关的定量值信号，直到试验结果，而 PV 神经元即使在试验结果后也保持价信号。同样，PV，但不是 SST，神经元群体对奖励和惩罚表现出相反的反应。此外，PV 的失活，而不是 SST，神经元影响锥体神经元的结局反应和活动逆转。建模提示 PV 神经元对奖励和惩罚的相反反应是促进快速线索-结果偶然性学习的有效机制。我们的结果表明 mPFC PV 神经元在快速更新值和 SST 神经元在预测即将发生的事件值中的主要作用。
METHODS::In recent years, transcranial electrical stimulation (tES) has been used to improve cognitive and perceptual abilities and to boost learning. In the visual domain, transcranial random noise stimulation (tRNS), a type of tES in which electric current is randomly alternating in between two electrodes at high frequency, has shown potential in inducing long lasting perceptual improvements when coupled with tasks such as contrast detection. However, its cortical mechanisms and online effects have not been fully understood yet, and it is still unclear whether these long-term improvements are due to early-stage perceptual enhancements of contrast sensitivity or later stage mechanisms such as learning consolidation. Here we tested tRNS effects on multiple spatial frequencies and orientation, showing that tRNS enhances detection of a low contrast Gabor, but only for oblique orientation and high spatial frequency (12 cycles per degree of visual angle). No improvement was observed for low contrast and vertical stimuli. These results indicate that tRNS can enhance contrast sensitivity already after one training session, however this early onset is dependent on characteristics of the stimulus such as spatial frequency and orientation. In particular, the shallow depth of tRNS is likely to affect superficial layers of the visual cortex where neurons have higher preferred spatial frequencies than cells in further layers, while the lack of effect on vertical stimuli might reflect the optimization of the visual system to see cardinally oriented low contrast stimuli, leaving little room for short-term improvement. Taken together, these results suggest that online tRNS effects on visual perception are the result of a complex interaction between stimulus intensity and cortical anatomy, consistent with previous literature on brain stimulation.
METHODS:OBJECTIVE:There is growing interest in treating diseases by electrical stimulation and block of peripheral autonomic nerves, but a paucity of studies on excitation and block of small diameter autonomic axons. We conducted in vivo quantification of the strength-duration properties, activity-dependent slowing (ADS), and responses to kilohertz frequency (KHF) signals for the rat vagus nerve (VN). APPROACH:We conducted acute in vivo experiments in urethane-anesthetised rats. We placed two cuff electrodes on the left cervical VN and one cuff electrode on the anterior subdiaphragmatic VN. The rostral cervical cuff was used to deliver pulses to quantify recruitment and ADS. The caudal cervical cuff was used to deliver KHF signals. The subdiaphragmatic cuff was used to record compound action potentials (CAPs). MAIN RESULTS:We quantified the input-output recruitment and strength-duration curves. Fits to the data using standard strength-duration equations were qualitatively similar, but the resulting chronaxie and rheobase estimates varied substantially. We measured larger thresholds for the slowest fibres (0.5 to 1 m/s), especially at shorter pulse widths. Using a novel cross-correlation CAP-based analysis, we measured ADS of ~2.3% after 3 min of 2 Hz stimulation, which is comparable to ADS reported for sympathetic efferents in somatic nerves, but much smaller than ADS in cutaneous nociceptors. We found greater ADS with higher stimulation frequency and non-monotonic changes in CV in select cases. We found monotonically increasing block thresholds across frequencies from 10 to 80 kHz for both fast and slow fibres. Further, following 25 s of KHF signal, neural conduction could require tens of seconds to recover. SIGNIFICANCE:The quantification of mammalian autonomic nerve responses to conventional and KHF signals provides essential information for development of peripheral nerve stimulation therapies and for understanding their mechanisms of action.
METHODS:BACKGROUND:Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM). METHODS:We report the clinical and stimulation characteristics of three patients with left hemispheric language dominance who demonstrate forced thought with functional mapping. To examine the brain networks underlying this phenomenon, we used the regions of interest (ROI) centered at the active electrode pairs. We modeled functional networks using two approaches: (1) rs-fMRI functional connectivity analysis, representing 81 healthy controls and (2) meta-analytic connectivity modeling (MACM), representing 8260 healthy subjects. We also determined the overlapping regions between these three subjects' rs-fMRI and MACM networks through a conjunction analysis. RESULTS:We identified that left PFC was associated with a large-scale functional network including frontal, temporal, and parietal regions, a network that has been associated with multiple cognitive functions including semantics, speech, attention, working memory, and explicit memory. CONCLUSIONS:We illustrate the neural networks involved in conceptual thought through a unique patient population and argue that PFC supports this function through activation of a widespread network.