Paramecium is a unicellular organism that swims in fresh water by beating thousands of cilia. When it is stimulated (mechanically, chemically, optically, thermally…), it often swims backward then turns and swims forward again. This “avoiding reaction” is triggered by a calcium-based action potential. For this reason, some authors have called Paramecium a “swimming neuron.” This review summarizes current knowledge about the physiological basis of behavior of Paramecium . Significance Statement Paramecium is a unicellular organism that swims in fresh water by beating thousands of cilia. When it is stimulated (mechanically, chemically, optically, thermally…), it often swims backward then turns and swims forward again. This “avoiding reaction” is triggered by a calcium-based action potential. For this reason, some authors have called Paramecium a “swimming neuron.” This review summarizes current knowledge about the physiological basis of behavior of Paramecium .

Qiaoling Cui, Xixun Du, Isaac Y. M. Chang, Arin Pamukcu, Varoth Lilascharoen, et al. (see pages [3966–3987][1]) The dorsal striatum is involved in action selection and sequencing. Whereas the dorsomedial subdivision is thought to mediate goal-directed actions, the dorsolateral subdivision is

The serotonergic system is strongly implicated in anxiety and depression, and it is the first-line target for pharmacological treatment ([Tamblyn et al., 2019][1]). Genetic factors predispose people to these disorders, but the anatomic and molecular diversity of the main serotonergic nuclei, the

The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and their roles in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting response of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson's disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a...

To thrive in dynamic environments, animals must be capable of rapidly and flexibly adapting behavioral responses to a changing context and internal state. Examples of behavioral flexibility include faster stimulus responses when attentive and slower responses when distracted. Contextual or state-dependent modulations may occur early in the cortical hierarchy and may be implemented via top-down projections from corticocortical or neuromodulatory pathways. However, the computational mechanisms mediating the effects of such projections are not known. Here, we introduce a theoretical framework to classify the effects of cell type-specific top-down perturbations on the information processing speed of cortical circuits. Our theory demonstrates that perturbation effects on stimulus processing can be predicted by intrinsic gain modulation, which controls the timescale of the circuit dynamics. Our theory leads to counterintuitive effects, such as improved performance with increased input variance. We tested the mod...

Understanding how and where in the brain sentence-level meaning is constructed from words presents a major scientific challenge. Recent advances have begun to explain brain activation elicited by sentences using vector models of word meaning derived from patterns of word co-occurrence in text corpora. These studies have helped map out semantic representation across a distributed brain network spanning temporal, parietal, and frontal cortex. However, it remains unclear whether activation patterns within regions reflect unified representations of sentence-level meaning, as opposed to superpositions of context-independent component words. This is because models have typically represented sentences as “bags-of-words” that neglect sentence-level structure. To address this issue, we interrogated fMRI activation elicited as 240 sentences were read by 14 participants (9 female, 5 male), using sentences encoded by a recurrent deep artificial neural-network trained on a sentence inference task (InferSent). Recurrent...

Sleep has been shown to be critical for memory consolidation, with some research suggesting that certain memories are prioritized for consolidation. Initial strength of a memory appears to be an important boundary condition in determining which memories are consolidated during sleep. However, the role of consolidation-mediating oscillations, such as sleep spindles and slow oscillations, in this preferential consolidation has not been explored. Here, 54 human participants (76% female) studied pairs of words to three distinct encoding strengths, with recall being tested immediately following learning and again 6 h later. Thirty-six had a 2 h nap opportunity following learning, while the remaining 18 remained awake throughout. Results showed that, across 6 h awake, weakly encoded memories deteriorated the fastest. In the nap group, however, this effect was attenuated, with forgetting rates equivalent across encoding strengths. Within the nap group, consolidation of weakly encoded items was associated with fas...

At the request of the authors, The Journal of Neuroscience is retracting “The Sustained Antidepressant Effects of Ketamine are Independent of the Lateral Habenula,” by Xuelong Zhou, Chenjing Zhang, Jiamin Miao, Ziyang Chen, Hongquan Dong, and Cunming Liu, which appears on pages [4131–4140][1]

Zebrafish models are used increasingly to study the molecular pathogenesis of Parkinson's disease (PD), owing to the extensive array of techniques available for their experimental manipulation and analysis. The ascending dopaminergic projection from the posterior tuberculum (TPp; diencephalic populations DC2 and DC4) to the subpallium is considered the zebrafish correlate of the mammalian nigrostriatal projection, but little is known about the neurophysiology of zebrafish DC2/4 neurons. This is an important knowledge gap, because autonomous activity in mammalian substantia nigra (SNc) dopaminergic neurons contributes to their vulnerability in PD models. Using a new transgenic zebrafish line to label living dopaminergic neurons, and a novel brain slice preparation, we conducted whole-cell patch clamp recordings of DC2/4 neurons from adult zebrafish of both sexes. Zebrafish DC2/4 neurons share many physiological properties with mammalian dopaminergic neurons, including the cell-autonomous generation of actio...

We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1+ class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1+ classes. By combining optogenetics and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highl...