Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction

Goal-directed behaviors are essential for normal function and significantly impaired in neuropsychiatric disorders. Despite extensive associations between genetic mutations and these disorders, the molecular contributions to goal-directed dysfunction remain unclear. We examined mice with constitutive and brain region-specific mutations in Neurexin1α, a neuropsychiatric disease-associated synaptic molecule, in value-based choice paradigms. We found Neurexin1α knockouts exhibited reduced selection of beneficial outcomes and impaired avoidance of costlier options. Reinforcement modeling suggested that this was driven by deficits in updating and representation of value. Disruption of Neurexin1α within telencephalic excitatory projection neurons, but not thalamic neurons, recapitulated choice abnormalities of global Neurexin1α knockouts. Furthermore, this selective forebrain excitatory knockout of Neurexin1α perturbed value-modulated neural signals within striatum, a central node in feedback-based reinforcement learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in value-modulated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

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Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers

Translational Psychiatry ◽

10.1038/s41398-021-01566-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiao Lin ◽

Jiahui Deng ◽

Kai Yuan ◽

Qiandong Wang ◽

Lin Liu ◽

...

Keyword(s):

Neural Activity ◽

Neural Substrates ◽

Brain Regions ◽

Reward Processing ◽

Memory Reconsolidation ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Postcentral Gyrus ◽

Propranolol Group ◽

Propranolol Administration

AbstractThe majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

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Amino Acids as Gustatory Stimuli in the Rat

The Journal of General Physiology ◽

10.1085/jgp.45.4.681 ◽

1962 ◽

Vol 45 (4) ◽

pp. 681-701 ◽

Cited By ~ 33

Author(s):

Bruce P. Halpern ◽

Rudy A. Bernard ◽

Morley R. Kare

Keyword(s):

Amino Acids ◽

Neural Activity ◽

Receptor Site ◽

Chorda Tympani ◽

Chorda Tympani Nerve ◽

High Concentration ◽

Low Concentration ◽

Common Receptor ◽

Amino Acid Solutions ◽

Selection Of

Neural activity in intact chorda tympani nerve of rats was studied with an electronic summator. Neural activity increased when amino acid solutions 0.01 M or above passed over the tongue. Response magnitude, at concentrations close to solubility limits for the amino acids tested, was: DL-methionine < DL-tryptophan < DL-valine < DL-alanine < glycine < 0.1 M NaCl. Maximum response magnitudes to 1 M D-, and 1.2 M DL-alanine, and 1.5 M glycine developed in 1 to 3 minutes. Following such stimulation, a 63 per cent reduction in response to 0.1 M NaCl occurred 60 minutes after the first stimulation (medians). The depression was still present 20 hours later. Responses to glycine and alanine were not depressed. Amino acids vs. water preferences were investigated. With ascending concentration sequences, rats selected low concentration DL- and L-alanine and glycine; accepted D-, L-, and DL-tryptophan and low concentration DL-methionine; and rejected high concentration glycine, DL-alanine, and DL-methionine. Descending sequences showed depressed and delayed selection of glycine and DL-alanine, and DL-methionine and D- and L-tryptophan rejection. Both groups rejected DL-valine. It is concluded that glycine and alanine receptor effects differ from those of NaCl, but that all three compounds may affect a common receptor site. Prior exposure to amino acids may modify subsequent neural and/or behavioral responses.

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Interpersonal Comparison of Utility by Measuring Neural Activity

10.1101/2021.06.04.447048 ◽

2021 ◽

Author(s):

Kaosu Matsumori ◽

Kazuki Iijima ◽

Yukihito Yomogida ◽

Kenji Matsumoto

Keyword(s):

Neural Activity ◽

Optimal Taxation ◽

Cost Benefit ◽

Third Party ◽

Impossibility Theorem ◽

Interpersonal Comparison ◽

Neural Signals ◽

Collective Decisions ◽

Economic Goods ◽

Household Incomes

Aggregating welfare across individuals to reach collective decisions is one of the most fundamental problems in our society. Interpersonal comparison of utility is pivotal and inevitable for welfare aggregation, because if each person's utility is not interpersonally comparable, there is no rational aggregation procedure that simultaneously satisfies even some very mild conditions for validity (Arrow's impossibility theorem). However, scientific methods for interpersonal comparison of utility have thus far not been available. Here, we have developed a method for interpersonal comparison of utility based on brain signals, by measuring the neural activity of participants performing gambling tasks. We found that activity in the medial frontal region was correlated with changes in expected utility, and that, for the same amount of money, the activity evoked was larger for participants with lower household incomes than for those with higher household incomes. Furthermore, we found that the ratio of neural signals from lower-income participants to those of higher-income participants coincided with estimates of their psychological pleasure by "impartial spectators", i.e. disinterested third-party participants satisfying specific conditions. Finally, we derived a decision rule based on aggregated welfare from our experimental data, and confirmed that it was applicable to a distribution problem. These findings suggest that our proposed method for interpersonal comparison of utility enables scientifically reasonable welfare aggregation by escaping from Arrow's impossibility and has implications for the fair distribution of economic goods. Our method can be further applied for evidence-based policy making in nations that use cost-benefit analyses or optimal taxation theory for policy evaluation.

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Categorizing and Individuating Others: The Neural Substrates of Person Perception

Journal of Cognitive Neuroscience ◽

10.1162/0898929042947801 ◽

2004 ◽

Vol 16 (10) ◽

pp. 1785-1795 ◽

Cited By ~ 43

Author(s):

Malia F. Mason ◽

C. Neil Macrae

Keyword(s):

Neural Activity ◽

Person Perception ◽

Social Cognitive ◽

Right Hemisphere ◽

Neural Substrates ◽

Hemispheric Differences ◽

Cognitive Operations ◽

Processing Abilities ◽

Group Members ◽

The Right

People are remarkably adroit at understanding other social agents. Quite how these information-processing abilities are realized, however, remains open to debate and empirical scrutiny. In particular, little is known about basic aspects of person perception, such as the operations that support people's ability to categorize (i.e., assign persons to groups) and individuate (i.e., discriminate among group members) others. In an attempt to rectify this situation, the current research focused on the initial perceptual stages of person construal and considered: (i) hemispheric differences in the efficiency of categorization and individuation; and (ii) the neural activity that supports these social-cognitive operations. Noting the greater role played by configural processing in individuation than categorization, it was expected that performance on the former task would be enhanced when stimuli (i.e., faces) were presented to the right rather than to the left cerebral hemisphere. The results of two experiments (Experiment 1—healthy individuals; Experiment 2—split-brain patient) confirmed this prediction. Extending these findings, a final neuroimaging investigation revealed that individuation is accompanied by neural activity in regions of the temporal and prefrontal cortices, especially in the right hemisphere. We consider the implications of these findings for contemporary treatments of person perception.

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The effects of V4 and middle temporal (MT) area lesions on visual performance in the rhesus monkey

Visual Neuroscience ◽

10.1017/s0952523800005423 ◽

1993 ◽

Vol 10 (4) ◽

pp. 717-746 ◽

Cited By ~ 142

Author(s):

Peter H. Schiller

Keyword(s):

Contrast Sensitivity ◽

Neural Activity ◽

Brightness Discrimination ◽

Reaction Times ◽

Neural System ◽

Extrastriate Cortex ◽

Middle Temporal ◽

Area V4 ◽

Form Vision ◽

Selection Of

AbstractThe effects of V4, MT, and combined V4+MT lesions were assessed on a broad range of visual capacities that included measures of contrast sensitivity, wavelength and brightness discrimination, form vision, pattern vision, motion and flicker perception, stereopsis, and the selection of stimuli that were less prominent than those with which they appeared in stimulus arrays. The major deficit observed was a loss in the ability, after V4 lesions, to select such less prominent stimuli; this was the case irrespective of the manner in which the stimulus arrays were made visible, using either luminance, chrominance, motion, or stereoscopic depth as surface media. In addition, V4 lesions yielded mild deficits in color, brightness, and form vision whereas MT lesions yielded mild to moderate deficits in motion and flicker perception. Both lesions produced mild deficits in contrast sensitivity, shape-from-motion perception, and yielded increased reaction times on many of the tasks. The impairment resulting from combined V4 and MT lesions was not greater than the sum of the deficits of either lesion. None of the lesions produced significant deficits in stereopsis. The findings suggest that (1) area V4 is part of a neural system that is involved in extracting stimuli from the visual scene that elicit less neural activity early in the visual system than do other stimuli with which they appear and (2) several other extrastriate regions and more than just two major cortical processing streams contribute to the processing of basic visual functions in the extrastriate cortex.

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“Modulation of apoptosis controls inhibitory interneuron number in the cortex”

10.1101/134916 ◽

2017 ◽

Author(s):

Myrto Denaxa ◽

Guilherme Neves ◽

Adam Rabinowitz ◽

Sarah Kemlo ◽

Petros Liodis ◽

...

Keyword(s):

Physiological State ◽

Inhibitory Interneuron ◽

Projection Neurons ◽

Activity Levels ◽

Cortical Interneurons ◽

A Cell ◽

Cell Type Specific ◽

Excitatory Projection ◽

Cortical Excitation ◽

The Right

AbstractCortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window. Here, we provide evidence that the extent of CI apoptosis during this critical period is plastic, cell type specific and can be reduced in a cell autonomous manner by acute increases in neuronal activity. We propose that the physiological state of the emerging neural network controls the activity levels of local CIs to modulate their numbers in a homeostatic manner.

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Graphene-Based Electrode Materials for Neural Activity Detection

Materials ◽

10.3390/ma14206170 ◽

2021 ◽

Vol 14 (20) ◽

pp. 6170

Author(s):

Weichen Wei ◽

Xuejiao Wang

Keyword(s):

Neural Activity ◽

High Performance ◽

Electrode Materials ◽

Neurological Diseases ◽

Activity Detection ◽

Neural Signals ◽

Neural Electrode ◽

Neural Electrodes ◽

Wide Range

The neural electrode technique is a powerful tool for monitoring and regulating neural activity, which has a wide range of applications in basic neuroscience and the treatment of neurological diseases. Constructing a high-performance electrode–nerve interface is required for the long-term stable detection of neural signals by electrodes. However, conventional neural electrodes are mainly fabricated from rigid materials that do not match the mechanical properties of soft neural tissues, thus limiting the high-quality recording of neuroelectric signals. Meanwhile, graphene-based nanomaterials can form stable electrode–nerve interfaces due to their high conductivity, excellent flexibility, and biocompatibility. In this literature review, we describe various graphene-based electrodes and their potential application in neural activity detection. We also discuss the biological safety of graphene neural electrodes, related challenges, and their prospects.

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Integration of locomotion and auditory signals in the mouse inferior colliculus

10.1101/795872 ◽

2019 ◽

Author(s):

Yoonsun Yang ◽

Joonyeol Lee ◽

Gunsoo Kim

Keyword(s):

Inferior Colliculus ◽

Neural Activity ◽

Stimulus Presentation ◽

Sound Stimulus ◽

Frequency Selectivity ◽

Auditory Information ◽

Neural Signals ◽

Sound Processing ◽

Auditory Integration ◽

Evoked Activity

AbstractThe inferior colliculus (IC) is the major midbrain auditory integration center, where virtually all ascending auditory inputs converge. Although the IC has been extensively studied for sound processing, little is known about the neural activity of the IC in moving subjects, as frequently happens in natural hearing conditions. Here we show, by recording the IC neural activity in walking mice, the activity of IC neurons is strongly modulated by locomotion in the absence of sound stimulus presentation. Similar modulation was also found in deafened mice, demonstrating that IC neurons receive non-auditory, locomotion-related neural signals. Sound-evoked activity was attenuated during locomotion, and the attenuation increased frequency selectivity across the population, while maintaining preferred frequencies. Our results suggest that during behavior, integrating movement-related and auditory information is an essential aspect of sound processing in the IC.

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Spatially guided distractor suppression during visual search

10.1101/2020.07.25.220947 ◽

2020 ◽

Author(s):

Tobias Feldmann-Wüstefeld ◽

Marina Weinberger ◽

Edward Awh

Keyword(s):

Multivariate Analyses ◽

Target Selection ◽

Basic Question ◽

Spatial Gradient ◽

Selection Effects ◽

Theta Band ◽

Neural Signals ◽

Past Work ◽

Visual Encoding ◽

Selection Of

AbstractPast work has demonstrated that active suppression of salient distractors is a critical part of visual selection. Evidence for goal-driven suppression includes below-baseline visual encoding at the position of salient distractors (Gaspelin and Luck, 2015) and neural signals such as the Pd that track the position and number of distractors in the visual field (Feldmann-Wustefeld and Vogel, 2019). One basic question regarding distractor suppression is whether it is inherently spatial or nonspatial in character. Indeed, past work has shown that distractors evoke both spatial (Theeuwes, 1992) and nonspatial forms of interference (Folk and Remington, 1998), motivating a direct examination of whether space is integral to goal-driven distractor suppression. Here, we provide clear evidence for a spatial gradient of suppression surrounding salient singleton distractors. Replicating past work, both reaction time and neural indices of target selection improved monotonically as the distance between target and distractor increased. Importantly, these target selection effects were paralleled by a monotonic decline in the amplitude of the Pd, an electrophysiological index of distractor suppression. Moreover, multivariate analyses revealed spatially selective activity in the theta band that tracked the position of the target and – critically – revealed suppressed activity at spatial channels centered on distractor positions. Thus, goal-driven selection of relevant over irrelevant information benefits from a spatial gradient of suppression surrounding salient distractors.

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Active maintenance of eligibility trace in rodent prefrontal cortex

Scientific Reports ◽

10.1038/s41598-020-75820-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Dong-Hyun Lim ◽

Young Ju Yoon ◽

Eunsil Her ◽

Suehee Huh ◽

Min Whan Jung

Keyword(s):

Prefrontal Cortex ◽

Neuronal Activity ◽

Neural Activity ◽

Credit Assignment ◽

Neural Signals ◽

Active Maintenance ◽

Time Period ◽

Eligibility Trace ◽

Action Value ◽

Foraging Task

Abstract Even though persistent neural activity has been proposed as a mechanism for maintaining eligibility trace, direct empirical evidence for active maintenance of eligibility trace has been lacking. We recorded neuronal activity in the medial prefrontal cortex (mPFC) in rats performing a dynamic foraging task in which a choice must be remembered until its outcome on the timescale of seconds for correct credit assignment. We found that mPFC neurons maintain significant choice signals during the time period between action selection and choice outcome. We also found that neural signals for choice, outcome, and action value converge in the mPFC when choice outcome was revealed. Our results indicate that the mPFC maintains choice signals necessary for temporal credit assignment in the form of persistent neural activity in our task. They also suggest that the mPFC might update action value by combining actively maintained eligibility trace with action value and outcome signals.

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