Journal of Neuroscience最新文献

Sensory systems enable organisms to detect and respond to environmental signals relevant for their survival and reproduction. A crucial aspect of any sensory signal is its intensity; understanding how sensory signals guide behavior requires probing sensory system function across the range of stimulus intensities naturally experienced by an organism. In olfaction, defining the range of natural odorant concentrations is difficult. Odors are complex mixtures of airborne chemicals emitting from a source in an irregular pattern that varies across time and space, necessitating specialized methods to obtain an accurate measurement of concentration. Perhaps as a result, experimentalists often choose stimulus concentrations based on empirical considerations rather than with respect to ecological or behavioral context. Here, we attempt to determine naturally relevant concentration ranges for olfactory stimuli by reviewing and integrating data from diverse disciplines. We compare odorant concentrations used in experimental studies in rodents and insects with those reported in different settings including ambient natural environments, the headspace of natural sources, and within the sources themselves. We also compare these values to psychophysical measurements of odorant detection threshold in rodents, where thresholds have been extensively measured. Odorant concentrations in natural regimes rarely exceed a few parts per billion, while most experimental studies investigating olfactory coding and behavior exceed these concentrations by several orders of magnitude. We discuss the implications of this mismatch and the importance of testing odorants in their natural concentration range for understanding neural mechanisms underlying olfactory sensation and odor-guided behaviors.

Previous work has implicated the nucleus accumbens (NAc) in the regulation of effort, defined as the amount of work an animal is willing to perform for a given reward, but little is known about the specific contributions of neuronal populations within the NAc to effort regulation. In this study, using male and female mice, we examined the contributions of direct pathway and indirect pathway neurons in the NAc core using an operant effort regulation task, in which the effort requirement is the number of lever presses needed for earning a food reward. Using optogenetics, we manipulated the activity of direct pathway spiny projection neurons (dSPNs, dopamine D1-like, D1+) and indirect pathway SPNs (iSPNs, adenosine 2A receptor, A2A+). Activating dSPNs reduced lever pressing regardless of the effort requirement, as it elicited gnawing, a competing consummatory behavior. On the other hand, activating iSPNs in the NAc core (but not in the shell) reduced lever pressing in an effort-dependent manner: stimulation-induced reduction in performance was greater at higher press-to-reward ratio requirements. In contrast, optogenetically inhibiting NAc core iSPN output resulted in increased levels of effort exertion. Our results show that the indirect pathway output from the NAc core can bidirectionally regulate effort exertion.Significance statement Using bidirectional optogenetic manipulation to manipulate direct and indirect pathway neurons in the nucleus accumbens core, we found that activating the direct pathway neurons reduced lever pressing regardless of the effort requirement, as it elicited competing consummatory behaviors like gnawing. On the other hand, activating the indirect pathway neurons in the NAc core reduced lever pressing in an effort-dependent manner: stimulation-inducted reduction in performance was greater at higher press-to-reward ratio requirements.

Visual information can have different meanings across species and the same visual stimulus can drive appetitive or aversive behavior. The superior colliculus (SC), a visual center located in the midbrain has been involved in driving such behaviors. Within this structure, the wide-field vertical cell (WFV) is a conserved morphological cell-type that is present in species ranging from reptiles to cats (Basso et al., 2021). Here we report our investigation of the connectivity of the WFV, their visual responses and how these responses are modulated by locomotion in male and female laboratory mice. We also address the molecular definition of these cells and attempt to reconcile recent findings acquired by RNA sequencing of single cells in the SC with the Ntsr1-Cre GN209 transgenic mouse line which was previously used to investigate WFV. We use viral strategies to reveal WFV inputs and outputs and confirm their unique response properties using in vivo two-photon imaging. Among the stimuli tested, WFV prefer looming stimuli, a small moving spot, and upward moving visual stimuli. We find that only visual responses driven by a looming stimulus show a significant modulation by locomotion. We identify several inputs to the WFV as potential candidates for this modulation. These results suggest that WFV integrate information across multiple brain regions and are subject to behavioral modulation. Taken together, our results pave the way to elucidate the role of these neurons in visual behavior and allow us to interrogate the definition of cell-types in the light of new molecular definitions.Significant statement Understanding how neuronal response preferences emerge remains a fundamental goal in neuroscience. Our ability to target neuron subpopulations and their embedding in circuits has greatly evolved over the last decades with the development of new tools including transgenic mouse lines and RNA sequencing methods. Here we focus on wide-field vertical cells (WFV) which are found in the superior colliculus, a visual center in the midbrain that is highly conserved across species. Our findings challenge earlier definitions of this cell-type and reconcile them with more modern approaches. Due to their conservation and connectivity, WFV present a model of choice to investigate how neurons gain their response specificity and relationships between structure, function, implication in behavior and molecular profiles.

In most mammals, conspecific chemical cues that drive innate social and sexual behavior are detected by the vomeronasal organ (VNO) and processed in the accessory olfactory bulb (AOB). Chemosensory stimulation of vomeronasal sensory neurons (VSNs) at their microvillous dendritic knobs triggers, first, a local signal transduction and amplification cascade and, second, transformation of that signal into action potential (AP) discharge at the soma. Both processes ‒ signal transduction and AP generation ‒ involve local Ca²⁺ elevations in the knob and soma, respectively. Here, we revisit the somewhat still controversial functions of Ca²⁺-activated ion channels in both VSN compartments. In acute mouse VNO slices (of either sex), focal photorelease of Ca²⁺ reveals that VSN knob and soma both act as independent Ca²⁺ signaling compartments, in which Ca²⁺ elevations exert opposite effects. While Ca²⁺ signals in the knob drive an excitatory inward current, Ca²⁺ elevations in the soma primarily activate hyperpolarizing outward currents that silence VSNs. A substantial fraction of the latter current is mediated by SK and / or BK channels. Notably, SK channel activity strongly affects VSN firing. Together, our study reveals a diverse composition of Ca²⁺-activated currents in VSN somata and uncovers an unexpected role of SK channels in dampening excitability and, thus, in controlling VSN-to-AOB information transfer.Significance Statement Cytosolic Ca²⁺ signals play an important role in vomeronasal neuron function. Both sensory signal transduction and information transfer via action potentials involve transient Ca²⁺ elevations. Using local Ca²⁺ uncaging during single-cell electrophysiological recordings, we demonstrate that Ca²⁺-activated ion channels exert opposite functions during primary transduction versus action potential firing. Specifically, SK channels are primarily involved in dampening vomeronasal firing.

The orbitofrontal cortex (OFC) plays a crucial role in value-based decisions. While much is known about how OFC neurons represent values, far less is known about information encoded in OFC local field potentials (LFPs). LFPs are important because they can reflect subthreshold activity not directly coupled to spiking, and because they are potential targets for less invasive forms of brain-machine interface (BMI). We recorded neural activity in the OFC of male macaques performing a two-option value-based decision task. We compared the value- and decision-coding properties of high-gamma LFPs (HG, 50-150 Hz) to the coding properties of spiking multi-unit activity (MUA) recorded concurrently on the same electrodes. HG and MUA both represented the values of decision targets, but HG signals had value-coding features that were distinct from concurrently-measured MUA. On average HG amplitude increased monotonically with value, whereas in MUA the value encoding was net neutral on average. HG encoded a signal consistent with a comparison between target values, a signal which was negligible in MUA. In individual channels, HG could predict choice outcomes more accurately than MUA; however, when channels were combined in a population-based decoder, MUA was more accurate than HG. In summary, HG signals reveal value-coding features in OFC that could not be observed from spiking activity, including representation of value comparisons and more accurate behavioral predictions. These results have implications for the role of OFC in value-based decisions, and suggest that high-frequency LFPs may be a viable - or even preferable - target for BMIs to assist cognitive function.Significance statement High-frequency LFPs are often assumed to be a mere proxy for local spiking activity. This study finds evidence to the contrary in the OFC of monkeys making value-based decisions. With respect to decision mechanisms, the results challenge previous findings by suggesting a role for OFC in computing value comparisons, evident in a comparison signal encoded in HG but not spiking. More broadly, the results add to the growing evidence for spike/LFP dissociations in prefrontal cortex, and support the idea that HG signals are an important but overlooked resource for identifying neural computations in cognitive tasks. In addition, single-channel HG signals furnished more accurate predictions about choice behavior, supporting the potential use of HG signals in cognitive neural prosthetics.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder that can cause impairments in spatial cognition and memory. The hippocampus is thought to support spatial cognition through the activity of place cells, neurons with spatial receptive fields. Coordinated firing of place cell populations is organized by different oscillatory patterns in the hippocampus during specific behavioral states. Theta rhythms organize place cell populations during awake exploration. Sharp wave-ripples organize place cell population reactivation during waking rest. Here, we examined the coordination of CA1 place cell populations during active behavior and subsequent rest in a rat model of FXS (Fmr1 knockout rats). While the organization of individual place cells by the theta rhythm was normal, the coordinated activation of sequences of place cells during individual theta cycles was impaired in Fmr1 knockout rats. Further, the subsequent replay of place cell sequences was impaired during waking rest following active exploration. Together, these results expand our understanding of how genetic modifications that model those observed in FXS affect hippocampal physiology and suggest a potential mechanism underlying impaired spatial cognition in FXS.Significance Statement Fragile X Syndrome (FXS) is a neurodevelopmental disorder that can cause impaired memory and atypical spatial behaviors such as "elopement" (i.e., wandering off and becoming lost). Activity in the CA1 subregion of the hippocampus supports spatial memory and spatial cognition, making it an important candidate to study in the context of FXS; however, how neuronal population activity in CA1 is affected by FXS is poorly understood. In this study, we found that the coordination of populations of CA1 neurons during active behavior and waking rest was impaired in a rat model of FXS. These results reveal hippocampal physiological deficits that may contribute to cognitive impairments in FXS.

Auditory deviance detection, the neural process by which unexpected stimuli are identified within repetitive acoustic environments, is crucial for survival. While this phenomenon has been extensively studied in the cortex, recent evidence indicates that it also occurs in subcortical regions, including the inferior colliculus (IC). However, compared to animal studies, research on subcortical deviance detection in humans is often constrained by methodological limitations, leaving several important questions unanswered. This study aims to overcome some of these limitations by employing auditory brainstem responses (ABRs) to investigate the earliest neural correlates of deviance detection in humans, with a focus on the IC. We presented healthy participants of either sex with low- and high-frequency chirps in an oddball paradigm and observed significant deviance detection effects in the ABR, specifically when low-frequency chirps were used as deviants within a context of high-frequency standards. These effects manifested as larger and faster ABRs to deviant stimuli, with the strongest responses occurring at higher stimulation rates. Our findings suggest that the human IC exhibits rapid, stimulus-specific deviance detection with differential modulation of response amplitude and latency. The data indicate that the temporal dynamics of novelty detection in humans align well with the data reported in animals, helping to bridge the gap between animal and human research. By uncovering previously unknown characteristics of subcortical deviance detection in humans, this study highlights the value of ABR recordings with excellent temporal resolution in investigating subcortical deviance detection processes.Significance statement Auditory deviance detection enables the brain to identify unexpected stimuli in a repetitive environment, but its subcortical mechanisms in humans remain comparatively underexplored. Using auditory brainstem responses (ABRs), our study reveals two key findings about deviance detection in the human inferior colliculus (IC). First, we show subcortical deviance detection at latencies under 10 ms, bridging a longstanding gap between human and animal research. Second, deviance detection in the IC is rapid, emerging within three or fewer standard repetitions, with differential modulation of ABR amplitude and latency. These findings improve our understanding of the temporal dynamics of auditory processing in the human IC and highlight the value of ABR recordings in studying subcortical deviance detection mechanisms.

High-level perception results from interactions between hierarchical brain systems responsive to gradually increasing feature complexities. During reading, the initial evaluation of simple visual features in the early visual cortex (EVC) is followed by orthographic and lexical computations in the ventral occipitotemporal cortex (vOTC). While similar visual regions are engaged in tactile Braille reading in congenitally blind people, it is unclear whether the visual network maintains or reorganises its hierarchy for reading in this population. Combining fMRI and chronometric transcranial magnetic stimulation (TMS), our study revealed a clear correspondence between sighted and blind individuals (both male and female) on how their occipital cortices functionally supports reading and speech processing. Using fMRI, we first observed that vOTC, but not EVC, showed an enhanced response to lexical vs. non-lexical information in both groups and sensory modalities. Using TMS, we further found that, in both groups, the processing of written words and pseudowords was disrupted by the EVC stimulation at both early and late time windows. In contrast, the vOTC stimulation disrupted the processing of these written stimuli only when applied at late time windows, again in both groups. In the speech domain, we observed TMS effects only for meaningful words and only in the blind participants. Overall, our results suggest that, while the responses in the deprived visual areas might extend their functional response to other sensory modalities, the computational gradients between early and higher-order occipital regions are retained, at least for reading.Significance statement The sighted visual cortex hierarchically interprets visual signals, from simple visual features in the early visual cortex to complex features in higher-order visual areas. The blind visual cortex is known to respond to tactile and auditory information, but is a similar computational hierarchy used to process these signals? Here we showed that the blind visual cortex processes tactile reading in a spatiotemporal hierarchy strikingly similar to the hierarchy used by the sighted visual cortex to process visual reading. Intriguingly, the blind visual cortex seems additionally involved in the processing of spoken words. Our results suggest that the computational gradients between sensory-deprived early and higher-order areas are largely independent of visual experiences, despite their enhanced responses to crossmodal input.

Memory retrieval activates regions across the brain, including not only the hippocampus and medial temporal lobe (MTL), but also frontal, parietal, and lateral temporal cortical regions. What remains unclear, however, is how these regions communicate to organize retrieval-specific processing. Here, we elucidate the role of theta (3-8 Hz) synchronization, broadly implicated in memory function, during the spontaneous retrieval of episodic memories. Analyzing a dataset of 382 neurosurgical patients (213 male, 168 female, 1 unknown) implanted with intracranial electrodes who completed a free recall task, we find that synchronous networks of theta phase synchrony span the brain in the moments before spontaneous recall, in comparison to periods of deliberation and incorrect recalls. Hubs of the retrieval network, which systematically synchronize with other regions, appear throughout the prefrontal cortex and lateral and medial temporal lobes, as well as other areas. Theta synchrony increases appear more prominently for slow (3 Hz) theta than for fast (8 Hz) theta in the recall-deliberation contrast, but not in the encoding or recall-intrusion contrast, and theta power and synchrony positively correlate throughout the theta band. These results implicate diffuse brain-wide synchronization of theta rhythms, especially slow theta, in episodic memory retrieval.Significance Statement Analyzing intracranial recordings from 382 subjects who completed an episodic free recall experiment, we study the brain-wide theta synchrony effects of memory retrieval. The literature has not previously described the whole-brain regional distribution of these effects nor studied them with respect to intrusions. We show that a whole-brain theta synchrony effect marks the recall accuracy contrast, that distributed synchronous hubs constitute a whole-brain retrieval network, and that theta synchrony in the successful encoding, successful retrieval, and recall accuracy contrasts correlates positively with theta power increases at a region. These findings advance our understanding of the role and localization of theta synchrony effects during human memory retrieval.

Biological neural networks translate sensory information into neural code that is held in memory over long timescales. Theories for how this occurs often posit a functional role of neural oscillations. However, recent advances show that neural oscillations are often confounded with non-oscillatory, aperiodic neural activity. Here we analyze a dataset of intracranial human EEG recordings (N=13; 10 female) to test the hypothesis that aperiodic activity plays a role in visual memory, independent and distinct from oscillations. By leveraging a new approach to time-resolved parameterization of neural spectral activity, we find event-related changes in both oscillations and aperiodic activity during memory encoding. During memory encoding, aperiodic-adjusted alpha oscillatory power significantly decreases while, simultaneously, aperiodic neural activity "flattens out". These results provide novel evidence for task-related dynamics of both aperiodic and oscillatory activity in human memory, paving the way for future investigations into the unique functional roles of these two neural processes in human cognition.Significance Statement Neural oscillations have been extensively implicated in memory encoding. However, recent advances show that oscillations are often confounded with aperiodic activity, motivating further investigation of aperiodic dynamics in memory. Here we analyze a dataset of intracranial human EEG recordings to test the hypothesis that aperiodic activity plays a role in memory, distinct from oscillations. By leveraging a new approach to time-resolved spectral parameterization, we find event-related changes in both oscillations and aperiodic activity. Based on our observations, we posit a speculative role for aperiodic activity in cognition, complementary to that of neural oscillations, in a form of neural communication through aperiodic dynamics.