Neuronal Representations Research Articles

Mosaic representations of odors in the input and output layers of the mouse olfactory bulb.

The elementary stimulus features encoded by the olfactory system remain poorly understood. We examined the relationship between 1,666 physical-chemical descriptors of odors and the activity of olfactory bulb inputs and outputs in awake mice. Glomerular and mitral and tufted cell responses were sparse and locally heterogeneous, with only a weak dependence of their positions on physical-chemical properties. Odor features represented by ensembles of mitral and tufted cells were overlapping but distinct from those represented in glomeruli, which is consistent with an extensive interplay between feedforward and feedback inputs to the bulb. This reformatting was well described as a rotation in odor space. The physical-chemical descriptors accounted for a small fraction in response variance, and the similarity of odors in the physical-chemical space was a poor predictor of similarity in neuronal representations. Our results suggest that commonly used physical-chemical properties are not systematically represented in bulbar activity and encourage further searches for better descriptors of odor space.

Projection from the Amygdala to the Thalamic Reticular Nucleus Amplifies Cortical Sound Responses

SUMMARYMany forms of behavior require selective amplification of neuronal representations of relevant environmental signals. Emotional learning enhances sensory responses in the sensory cortex, yet the underlying circuits remain poorly understood. We identify a pathway between the basolateral amygdala (BLA), an emotional learning center in the mouse brain, and the inhibitory reticular nucleus of the thalamus (TRN). Optogenetic activation of BLA suppressed spontaneous, but not tone-evoked, activity in the auditory cortex (AC), amplifying tone-evoked responses. Viral tracing identified BLA projections terminating at TRN. Optogenetic activation of amygdala-TRN projections further amplified tone-evoked responses in the auditory thalamus and cortex. The results are explained by a computational model of the thalamocortical circuitry, in which activation of TRN by BLA primes thalamocortical neurons to relay relevant sensory input. This circuit mechanism shines a neural spotlight on behaviorally relevant signals and provides a potential target for the treatment of neuropsychological disorders.

Neuronal representation of environmental boundaries in egocentric coordinates

Movement through space is a fundamental behavior for all animals. Cognitive maps of environments are encoded in the hippocampal formation in an allocentric reference frame, but motor movements that comprise physical navigation are represented within an egocentric reference frame. Allocentric navigational plans must be converted to an egocentric reference frame prior to implementation as overt behavior. Here we describe an egocentric spatial representation of environmental boundaries in the dorsomedial striatum.

The expression of allocentric object-place recognition memory during development

The allocentric representation of space is a fundamental pillar of episodic experience. In infant rats, the neural circuitry underlying the formation of allocentric spatial representations is functioning from early on when eyes are opening, i.e., before postnatal day (PD) 15. However, it remains unclear when and how during early development rats use these representations to regulate spatial behavior. Here, we studied indicators of memory-based spatial navigation using a classical object-place recognition (OPR) task set-up in infant (PD15), pre-weanling (PD18), juvenile (PD25), peri-adolescent (PD31), adolescent (PD38, PD48), and young adult rats (PD84). On the task, rats explored an arena with two identical objects, and memory was tested in a recall phase 3 h later in the same arena with, one object displaced from its original location. Only at adolescence (PD38), rats showed the typical adult-like expression of allocentric spatial memory with a preferential exploration of the object at the novel location. However, the first expression of allocentric spatial memory was revealed already in PD18 rats, which contrasting with PD84 rats, showed a preference to explore the object at the familiar location. At PD31, rats showed a null preference between the object-locations. Nevertheless, spatial memory at this age expressed in a preference for the zone including the familiar object-location. In PD15 rats, we found no evidence for a memory-based organization of spatial behavior. In conclusion, although rats might be able to form allocentric neuronal representations of space already earlier, only from PD18 on, such representations are used to organize spatial behavior, with a motivational shift from familiarity to novelty-driven navigation occurring during adolescence.

Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.

Simple Acoustic Features Can Explain Phoneme-Based Predictions of Cortical Responses to Speech

SummaryWhen we listen to speech, we have to make sense of a waveform of sound pressure. Hierarchical models of speech perception assume that, to extract semantic meaning, the signal is transformed into unknown, intermediate neuronal representations. Traditionally, studies of such intermediate representations are guided by linguistically defined concepts, such as phonemes. Here, we argue that in order to arrive at an unbiased understanding of the neuronal responses to speech, we should focus instead on representations obtained directly from the stimulus. We illustrate our view with a data-driven, information theoretic analysis of a dataset of 24 young, healthy humans who listened to a 1 h narrative while their magnetoencephalogram (MEG) was recorded. We find that two recent results, the improved performance of an encoding model in which annotated linguistic and acoustic features were combined and the decoding of phoneme subgroups from phoneme-locked responses, can be explained by an encoding model that is based entirely on acoustic features. These acoustic features capitalize on acoustic edges and outperform Gabor-filtered spectrograms, which can explicitly describe the spectrotemporal characteristics of individual phonemes. By replicating our results in publicly available electroencephalography (EEG) data, we conclude that models of brain responses based on linguistic features can serve as excellent benchmarks. However, we believe that in order to further our understanding of human cortical responses to speech, we should also explore low-level and parsimonious explanations for apparent high-level phenomena.

Chronic Unilateral Hearing Loss Disrupts Neural Tuning to Sound-Source Azimuth in the Rat Primary Auditory Cortex.

Accurate sound localization requires normal binaural input and precise auditory neuronal representation of sound spatial locations. Previous studies showed that unilateral hearing loss profoundly impaired the sound localization abilities. However, the underlying neural mechanism is not fully understood. Here, we investigated how chronic unilateral conductive hearing loss (UCHL) affected the neural tuning to sound source azimuth in the primary auditory cortex (AI). The UCHL was manipulated by the removal of tympanic membrane and malleus in the right ear of young (P14) rats and adult (P57) rats. We recorded the azimuth tuning of neurons in the left AI contralateral to the operated ear in the two groups of rats that experienced 2 months of UCHL, and in the left AI of age-matched control rats. We found that AI neurons in control rats showed predominant preference to sound from contralateral azimuths. However, UCHL weakened the cortical neuronal representation of contralateral azimuths on the operated ear side and strengthened the cortical neuronal representation of ipsilateral azimuths on the intact ear side. This effect was stronger in rats with UCHL at young age than in rats with UCHL in adulthood. Moreover, UCHL degraded the azimuth selectivity and azimuth sensitivity of AI neurons, and this effect was stronger in rats with UCHL in adulthood than in rats with UCHL at young age. These findings highlight a remarkable age-related experience-dependent plasticity of neural tuning to sound source azimuth in AI, and imply a neural mechanism for the impacts of chronic UCHL on sound localization abilities.

Haunted by the past: old emotions remain salient in insomnia disorder.

Studies suggest that sleep supports persistent changes in the neuronal representation of emotional experiences such that they are remembered better and less distressful when recalled than when they were first experienced. It is conceivable that sleep fragmentation by arousals, a key characteristic of insomnia disorder, could hamper the downregulation of distress. In this study, we sought further support for the idea that insomnia disorder may involve a lasting deficiency to downregulate emotional distress. We used functional MRI in insomnia disorder (n = 27) and normal sleepers (n = 30) to identify how brain activation differs between novel and relived self-conscious emotions. We evaluated whether brain activity elicited by reliving emotional memories from the distant past resembles the activity elicited by novel emotional experiences more in insomnia disorder than in normal sleepers. Limbic areas were activated during novel shameful experiences as compared to neutral experiences in both normal sleepers and insomnia disorder. In normal sleepers, reliving of shameful experiences from the past did not elicit a limbic response. In contrast, participants with insomnia disorder recruited overlapping parts of the limbic circuit, in particular the dorsal anterior cingulate cortex, during both new and relived shameful experiences. The differential activity patterns with new and old emotions in normal sleepers suggest that reactivation of the long-term memory trace does not recruit the limbic circuit. The overlap of activations in insomnia disorder is in line with the hypothesis that the disorder involves a deficiency to dissociate the limbic circuit from the emotional memory trace. Moreover, the findings provide further support for a role of the anterior cingulate cortex in insomnia.

Contribution of Sensory Encoding to Measured Bias.

Signal detection theory (SDT) is a widely used theoretical framework that describes how variable sensory signals are integrated with a decision criterion to support perceptual decision-making. SDT provides two key measurements: sensitivity (d') and bias (c), which reflect the separability of decision variable distributions (signal and noise) and the position of the decision criterion relative to optimal, respectively. Although changes in the subject's decision criterion can be reflected in changes in bias, decision criterion placement is not the sole contributor to measured bias. Indeed, neuronal representations of bias have been observed in sensory areas, suggesting that some changes in bias are because of effects on sensory encoding. To directly test whether the sensory encoding process can influence bias, we optogenetically manipulated neuronal excitability in primary visual cortex (V1) in mice of both sexes during either an orientation discrimination or a contrast detection task. Increasing excitability in V1 significantly decreased behavioral bias, whereas decreasing excitability had the opposite effect. To determine whether this change in bias is consistent with effects on sensory encoding, we made extracellular recordings from V1 neurons in passively viewing mice. Indeed, we found that optogenetic manipulation of excitability shifted the neuronal bias in the same direction as the behavioral bias. Moreover, manipulating the quality of V1 encoding by changing stimulus contrast or interstimulus interval also resulted in consistent changes in both behavioral and neuronal bias. Thus, changes in sensory encoding are sufficient to drive changes in bias measured using SDT.SIGNIFICANCE STATEMENT Perceptual decision-making involves sensory integration followed by application of a cognitive criterion. Using signal detection theory, one can extract features of the underlying decision variables and rule: sensitivity (d') and bias (c). Because bias is measured as the difference between the optimal and actual criterion, it is sensitive to both the sensory encoding processes and the placement of the decision criterion. Here, we use behavioral and electrophysiological approaches to demonstrate that measures of bias depend on sensory processes. Optogenetic manipulations of V1 in mice bidirectionally affect both behavioral and neuronal measures of bias with little effect on sensitivity. Thus, changes in sensory encoding influence bias, and the absence of changes in sensitivity do not preclude changes in sensory encoding.

A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space

SummaryRetrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Hippocampal pyramidal cells (PYRs) of the mammalian brain provide mnemonic representations of space. Yet the substrates by which these hippocampal representations support memory-guided behavior remain unknown. Here, we uncover a direct connection from dorsal CA1 (dCA1) hippocampus to nucleus accumbens (NAc) that enables the behavioral manifestation of place-reward memories. By monitoring neuronal ensembles in mouse dCA1→NAc pathway, combined with cell-type selective optogenetic manipulations of input-defined postsynaptic neurons, we show that dCA1 PYRs drive NAc medium spiny neurons and orchestrate their spiking activity using feedforward inhibition mediated by dCA1-connected parvalbumin-expressing fast-spiking interneurons. This tripartite cross-circuit motif supports spatial appetitive memory and associated NAc assemblies, being independent of dorsal subiculum and dispensable for both spatial novelty detection and reward seeking. Our findings demonstrate that the dCA1→NAc pathway instantiates a limbic-motor interface for neuronal representations of space to promote effective appetitive behavior.

Effects of self-locomotion on the activity of place cells in the hippocampus of a freely behaving monkey

The activity of hippocampal cell assemblies is considered to function as the neural substrate for a cognitive map in various animal species. The firing rate of hippocampal place cells increases when an individual animal reaches a specific location in an environment. Although cumulative views on place cells have been revealed by studies using rodents under free-behavior conditions, few studies have addressed the spatial representation provided by hippocampal neurons in primates. Moreover, although previous work in rats has demonstrated the importance of locomotion velocity and direction in the spatially selective discharge of hippocampal neurons, it remains unknown whether a corresponding phenomenon exists in the primate hippocampus. In the present study, we recorded the activity and investigated the spatial representation of the hippocampal neurons in a freely behaving monkey performing a shuttle-movement task. We observed increased activity in a subset of hippocampal neurons (place cells) when the monkey crossed a particular location. Many of the monkey place cells exhibited sensitivity to locomotion velocity rather than to locomotion direction. These results suggest the existence of primate hippocampal place cells comparable to those in rodents, with the exception that, in primates, velocity information has a stronger impact on place cell activity than directional information.

Dendritic, Cellular and Circuit Mechanisms of Spatial Representations

How are neuronal representations of the spatial environment generated at the level of synapses, neurons, and neuronal circuits? Neurons in the hippocampal formation produce striking spatial firing patterns that may provide the brain with a cognitive map of the environment. We have combined computational modelling, in vivo and in vitro recordings to understand how spatially modulated firing is generated at the synaptic, cellular and network level. We address this question in several key circuits that are critical for spatial cognition and memory, such as the medial entorhinal cortex and the dentate gyrus. We find that in both regions, nonlinear properties of individual neurons can specifically contribute to the computations performed by these circuits: In the medial entorhinal cortex, nonlinear integration can sharpen the precision of the temporal code and enhance the robustness of the rate code of grid cell firing, whereas in the dentate gyrus, nonlinear properties of individual neurons can help to distinguish between similar synaptic inputs patterns.

Differences in Neuronal Representation of Mental Rotation in Patients With Complex Regional Pain Syndrome and Healthy Controls

Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Because the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in the neural representation of MR occur between patients with CRPS and healthy controls (HC). Therefore, we included 15 patients with chronic CRPS and 15 age- and gender-matched HC. We assessed behavioral (accuracy and reaction time for MR of both hands), clinical (Disabilities of Arm, Shoulder and Hand questionnaire) and magnetic resonance imaging (T1-weighted, function magnetic resonance imaging during MR) data. Reaction times in the patient group were delayed compared with HC without a lateralization effect for the affected hand side. Although both groups showed an activation pattern typical for MR, only HC showed a highly significant contrast for the rotated versus unrotated hands in the right intraparietal sulcus. Patients with CRPS showed a reduction of functional magnetic resonance imaging activation in areas including the subthalamic nucleus, nucleus accumbens, and putamen. Regression analysis for the CRPS group emphasized the importance of putamen and nucleus accumbens activation for MR performance. This study highlights the reduced access of patients with CRPS for mental resources modulating arousal, emotional response, and subcortical sensorimotor integration. PerspectiveThis study localized the underlying neural responses for impaired mental rotation in patients with complex regional pain syndrome as a decrease in basal ganglia (putamen) and nucleus accumbens activation.

Odorant Receptor Inhibition is Fundamental to Odor Encoding

Most natural odors are complex mixtures of many volatile components, competing to bind odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) of the nose. To date surprisingly little is known about how OR antagonism shapes neuronal representations in the periphery of the olfactory system. Here, we investigated its prevalence, the degree to which it disrupts OR ensemble activity, and its conservation across related ORs. Calcium imaging microscopy of dissociated OSNs revealed significant inhibition, often complete attenuation, of responses to indole, a commonly occurring volatile associated with both floral and fecal odors, by a set of 36 tested odorants. To confirm an OR mechanism for the observed inhibition, we performed single-cell transcriptomics on OSNs that exhibited specific response profiles to a diagnostic panel of odorants and identified the receptor Olfr743 which, when tested in vitro, recapitulated ex vivo responses. We screened ten ORs from the Olfr743 clade with 800 perfumery-related odorants spanning a range of chemical scaffolds and functional groups, over half of which (430) antagonized at least one of the ten ORs. Furthermore, OR activity outcomes were divergent rather than redundant, even for the most closely related paralogs. OR activity fitted a mathematical model of competitive receptor binding and suggests that normalization of OSN ensemble responses to odorant mixtures is the rule rather than the exception. In summary, we observed OR antagonism, inverse agonism and partial agonism occurring frequently and in a combinatorial manner. Thus, extensive receptor-mediated computation of mixture information appears to occur in the olfactory epithelium prior to transmission of odor information to the olfactory bulb.

Auditory-induced response in the primary sensory cortex of rodents.

The details of auditory response at the subthreshold level in the rodent primary somatosensory cortex, the barrel cortex, have not been studied extensively, although several phenomenological reports have been published. Multisensory features may act as neuronal representations of links between inputs from one sensory modality to other sensory modalities. Here, we examined the basic multisensory postsynaptic responses in the rodent barrel cortex using in vivo whole-cell recordings of neurons. We observed robust responses to acoustic stimuli in most barrel cortex neurons. Acoustically evoked responses were mediated by hearing and reached approximately 60% of the postsynaptic response amplitude elicited by strong somatosensory stimuli. Compared to tactile stimuli, auditory stimuli evoked postsynaptic potentials with a longer latency and longer duration. Specifically, auditory stimuli in barrel cortex neurons appeared to trigger “up states”, episodes associated with membrane depolarization and increased synaptic activity. Taken together, our data suggest that barrel cortex neurons have multisensory properties, with distinct synaptic mechanisms underlying tactile and non-tactile responses.

A Method for the Symbolic Representation of Neurons.

The field of neuroanatomy has progressed considerably in recent decades, thanks to the emergence of novel methods which provide new insights into the organization of the nervous system. These new methods have produced a wealth of data that needs to be analyzed, shifting the bottleneck from the acquisition to the analysis of data. In other disciplines, such as in many engineering areas, scientists and engineers are dealing with increasingly complex systems, using hierarchical decompositions, graphical models and simplified schematic diagrams for analysis and design processes. This approach makes it possible for users to simultaneously combine global system views and very detailed representations of specific areas of interest, by selecting appropriate representations for each of these views. In this way, users can concentrate on specific details while also maintaining a general system overview — a capability that is essential for understanding structure and function whenever complexity is an issue. Following this approach, this paper focuses on a graphical tool designed to help neuroanatomists to better understand and detect morphological characteristics of neuronal cells. The method presented here, based on a symbolic representation that can be tailored to enhance a particular range of features of a neuron or neuron set, has proven to be useful for highlighting particular geometries that may be hidden due to the complexity of the analysis tasks and the richness of neuronal morphologies. A software tool has been developed to generate graphical representations of neurons from 3D computer-aided reconstruction files.

Memory entrainment by visually evoked theta-gamma coupling

The wake human brain constantly encodes novel information and integrates them into existing neuronal representations. It is posited that the formation of new memory traces is orchestrated by the synchronization of neuronal activity in the theta rhythm (3–8 Hz), theta coupled gamma activity (40–120 Hz), and decreases in the alpha rhythm (8–12 Hz). Critically, given the correlative nature of neurophysiological recordings, the functional relevance of oscillatory processes is not well understood. Here, we experimentally enhanced memory formation processes by a rhythmic visual stimulation at an individual theta frequency, in contrast to the stimulation at an individual alpha frequency. This memory entrainment effect was not explained by theta power per se, but was driven by a visually evoked theta-gamma coupling pattern. This underlines the functional role of the theta rhythm and the theta-gamma neuronal code in human episodic memory. The entrainment of mnemonic network mechanisms by a visual stimulation technique provides a proof of concept that visual pacemakers can entrain complex cognitive processes in the wake human brain.

Neuronal phase consistency tracks dynamic changes in acoustic spectral regularity.

The brain parses the auditory environment into distinct sounds by identifying those acoustic features in the environment that have common relationships (e.g., spectral regularities) with one another and then grouping together the neuronal representations of these features. Although there is a large literature that tests how the brain tracks spectral regularities that are predictable, it is not known how the auditory system tracks spectral regularities that are not predictable and that change dynamically over time. Furthermore, the contribution of brain regions downstream of the auditory cortex to the coding of spectral regularity is unknown. Here, we addressed these two issues by recording electrocorticographic activity, while human patients listened to tone-burst sequences with dynamically varying spectral regularities, and identified potential neuronal mechanisms of the analysis of spectral regularities throughout the brain. We found that the degree of oscillatory stimulus phase consistency (PC) in multiple neuronal-frequency bands tracked spectral regularity. In particular, PC in the delta-frequency band seemed to be the best indicator of spectral regularity. We also found that these regularity representations existed in multiple regions throughout cortex. This widespread reliable modulation in PC - both in neuronal-frequency space and in cortical space - suggests that phase-based modulations may be a general mechanism for tracking regularity in the auditory system specifically and other sensory systems more generally. Our findings also support a general role for the delta-frequency band in processing the regularity of auditory stimuli.

Efficient cortical coding of 3D posture in freely behaving rats.

Animals constantly update their body posture to meet behavioral demands, but little is known about the neural signals on which this depends. We therefore tracked freely foraging rats in three dimensions while recording from the posterior parietal cortex (PPC) and the frontal motor cortex (M2), areas critical for movement planning and navigation. Both regions showed strong tuning to posture of the head, neck, and back, but signals for movement were much less dominant. Head and back representations were organized topographically across the PPC and M2, and more neurons represented postures that occurred less often. Simultaneous recordings across areas were sufficiently robust to decode ongoing behavior and showed that spiking in the PPC tended to precede that in M2. Both the PPC and M2 strongly represent posture by using a spatially organized, energetically efficient population code.

Posture in the brain

Neuroscience Our understanding of the neural basis of motor control originates in studies of eye, hand, and arm movements in primates. Mimica et al. investigated neuronal representations of body postures in the posterior parietal and frontal motor cortices with three-dimensional tracking of freely moving rodents (see the Perspective by Chen). Both brain regions represented posture rather than movements and self-motion. Decoding the activity of neurons in the two regions accurately predicted an animal's posture. Science , this issue p. [584][1]; see also p. [520][2] [1]: /lookup/doi/10.1126/science.aau2013 [2]: /lookup/doi/10.1126/science.aav3819