Descending pathways increase sensory neural response heterogeneity to facilitate decoding and behavior.

The functional role of heterogeneous spiking responses of otherwise similarly tuned neurons to stimulation, which has been observed ubiquitously, remains unclear to date. Here, we demonstrate that such response heterogeneity serves a beneficial function that is used by downstream brain areas to generate behavioral responses that follows the detailed timecourse of the stimulus. Multi-unit recordings from sensory pyramidal cells within the electrosensory system of Apteronotus leptorhynchus were performed and revealed highly heterogeneous responses that were similar for all cell types. By comparing the coding properties of a given neural population before and after inactivation of descending pathways, we found that heterogeneities were beneficial as decoding was then more robust to the addition of noise. Taken together, our results not only reveal that descending pathways actively promote response heterogeneity within a given cell type, but also uncover a beneficial function for such heterogeneity that is used by the brain to generate behavior.

Population Coding of Natural Electrosensory Stimuli by Midbrain Neurons.

Natural stimuli display spatiotemporal characteristics that typically vary over orders of magnitude, and their encoding by sensory neurons remains poorly understood. We investigated population coding of highly heterogeneous natural electrocommunication stimuli in Apteronotus leptorhynchus of either sex. Neuronal activities were positively correlated with one another in the absence of stimulation, and correlation magnitude decayed with increasing distance between recording sites. Under stimulation, we found that correlations between trial-averaged neuronal responses (i.e., signal correlations) were positive and higher in magnitude for neurons located close to another, but that correlations between the trial-to-trial variability (i.e., noise correlations) were independent of physical distance. Overall, signal and noise correlations were independent of stimulus waveform as well as of one another. To investigate how neuronal populations encoded natural electrocommunication stimuli, we considered a nonlinear decoder for which the activities were combined. Decoding performance was best for a timescale of 6 ms, indicating that midbrain neurons transmit information via precise spike timing. A simple summation of neuronal activities (equally weighted sum) revealed that noise correlations limited decoding performance by introducing redundancy. Using an evolution algorithm to optimize performance when considering instead unequally weighted sums of neuronal activities revealed much greater performance values, indicating that midbrain neuron populations transmit information that reliably enable discrimination between different stimulus waveforms. Interestingly, we found that different weight combinations gave rise to similar discriminability, suggesting robustness. Our results have important implications for understanding how natural stimuli are integrated by downstream brain areas to give rise to behavioral responses.SIGNIFICANCE STATEMENT We show that midbrain electrosensory neurons display correlations between their activities and that these can significantly impact performance of decoders. While noise correlations limited discrimination performance by introducing redundancy, considering unequally weighted sums of neuronal activities gave rise to much improved performance and mitigated the deleterious effects of noise correlations. Further analysis revealed that increased discriminability was achieved by making trial-averaged responses more separable, as well as by reducing trial-to-trial variability by eliminating noise correlations. We further found that multiple combinations of weights could give rise to similar discrimination performances, which suggests that such combinatorial codes could be achieved in the brain. We conclude that the activities of midbrain neuronal populations can be used to reliably discriminate between highly heterogeneous stimulus waveforms.

Neural Synchrony Gives Rise to Amplitude- and Duration-Invariant Encoding Consistent With Perception of Natural Communication Stimuli.

When confronted with a highly variable environment, it remains poorly understood how neural populations encode and classify natural stimuli to give rise to appropriate and consistent behavioral responses. Here we investigated population coding of natural communication signals with different attributes (i.e., amplitude and duration) in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. Our results show that, while single peripheral neurons encode the detailed timecourse of different stimulus waveforms, measures of population synchrony are effectively unchanged because of coordinated increases and decreases in activity. A phenomenological mathematical model reproduced this invariance and shows that this can be explained by considering homogeneous populations whose responses are solely determined by single neuron firing properties. Moreover, recordings from downstream central neurons reveal that synchronous afferent activity is actually decoded and thus most likely transmitted to higher brain areas. Finally, we demonstrate that the associated behavioral responses at the organism level are invariant. Our results provide a mechanism by which amplitude- and duration-invariant coding of behaviorally relevant sensory input emerges across successive brain areas thereby presumably giving rise to invariant behavioral responses. Such mechanisms are likely to be found in other systems that share anatomical and functional features with the electrosensory system (e.g., auditory, visual, vestibular).

Descending pathways mediate adaptive optimized coding of natural stimuli in weakly electric fish.

Biological systems must be flexible to environmental changes to survive. This is exemplified by the fact that sensory systems continuously adapt to changes in the environment to optimize coding and behavioral responses. However, the nature of the underlying mechanisms remains poorly understood in general. Here, we investigated the mechanisms mediating adaptive optimized coding of naturalistic stimuli with varying statistics depending on the animal's velocity during movement. We found that central neurons adapted their responses to stimuli with different power spectral densities such as to optimally encode them, thereby ensuring that behavioral responses are, in turn, better matched to the new stimulus statistics. Sensory adaptation further required descending inputs from the forebrain as well as the raphe nuclei. Our findings thus reveal a previously unknown functional role for descending pathways in mediating adaptive optimized coding of natural stimuli that is likely generally applicable across sensory systems and species.

Encoding and Perception of Electro-communication Signals in Apteronotus leptorhynchus.

Animal communication plays an essential role in triggering diverse behaviors. It is believed in this regard that signal production by a sender and its perception by a receiver is co-evolving in order to have beneficial effects such as to ensure that conspecifics remain sensitive to these signals. However, in order to give appropriate responses to a communication signal, the receiver has to first detect and interpret it in a meaningful way. The detection of communication signals can be limited under some circumstances, for example when the signal is masked by the background noise in which it occurs (e.g., the cocktail-party problem). Moreover, some signals are very alike despite having different meanings making it hard to discriminate between them. How the central nervous system copes with these tasks and problems is a central question in systems neuroscience. Gymnotiform weakly electric fish pose an interesting system to answer these questions for various reasons: (1) they use a variety of communication signals called "chirps" during different behavioral encounters; (2) the central physiology of the electrosensory system is well known; and (3) most importantly, these fish give reliable behavioral responses to artificial stimuli that resemble natural communication signals, making it possible to uncover the neural mechanisms that lead to the observed behaviors.

Feedback optimizes neural coding and perception of natural stimuli.

Growing evidence suggests that sensory neurons achieve optimal encoding by matching their tuning properties to the natural stimulus statistics. However, the underlying mechanisms remain unclear. Here we demonstrate that feedback pathways from higher brain areas mediate optimized encoding of naturalistic stimuli via temporal whitening in the weakly electric fish Apteronotus leptorhynchus. While one source of direct feedback uniformly enhances neural responses, a separate source of indirect feedback selectively attenuates responses to low frequencies, thus creating a high-pass neural tuning curve that opposes the decaying spectral power of natural stimuli. Additionally, we recorded from two populations of higher brain neurons responsible for the direct and indirect descending inputs. While one population displayed broadband tuning, the other displayed high-pass tuning and thus performed temporal whitening. Hence, our results demonstrate a novel function for descending input in optimizing neural responses to sensory input through temporal whitening that is likely to be conserved across systems and species.

Weakly electric fish distinguish between envelope stimuli arising from different behavioral contexts.

Understanding how sensory information is processed by the brain in order to give rise to behavior remains poorly understood in general. Here, we investigated the behavioral responses of the weakly electric fish Apteronotus albifrons to stimuli arising from different contexts, by measuring changes in the electric organ discharge (EOD) frequency. Specifically, we focused on envelopes, which can arise either because of movement (i.e. motion envelopes) or because of interactions between the electric fields of three of more fish (i.e. social envelopes). Overall, we found that the animal's EOD frequency effectively tracked the detailed time course of both motion and social envelopes. In general, behavioral sensitivity (i.e. gain) decreased while phase lag increased with increasing envelope and carrier frequency. However, changes in gain and phase lag as a function of changes in carrier frequency were more prominent for motion than for social envelopes in general. Importantly, we compared behavioral responses to motion and social envelopes with similar characteristics. Although behavioral sensitivities were similar, we observed an increased response lag for social envelopes, primarily for low carrier frequencies. Thus, our results imply that the organism can, based on behavioral responses, distinguish envelope stimuli resulting from movement from those that instead result from social interactions. We discuss the implications of our results for neural coding of envelopes and propose that behavioral responses to motion and social envelopes are mediated by different neural circuits in the brain.

Descending pathways generate perception of and neural responses to weak sensory input.

Natural sensory stimuli frequently consist of a fast time-varying waveform whose amplitude or contrast varies more slowly. While changes in contrast carry behaviorally relevant information necessary for sensory perception, their processing by the brain remains poorly understood to this day. Here, we investigated the mechanisms that enable neural responses to and perception of low-contrast stimuli in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We found that fish reliably detected such stimuli via robust behavioral responses. Recordings from peripheral electrosensory neurons revealed stimulus-induced changes in firing activity (i.e., phase locking) but not in their overall firing rate. However, central electrosensory neurons receiving input from the periphery responded robustly via both phase locking and increases in firing rate. Pharmacological inactivation of feedback input onto central electrosensory neurons eliminated increases in firing rate but did not affect phase locking for central electrosensory neurons in response to low-contrast stimuli. As feedback inactivation eliminated behavioral responses to these stimuli as well, our results show that it is changes in central electrosensory neuron firing rate that are relevant for behavior, rather than phase locking. Finally, recordings from neurons projecting directly via feedback to central electrosensory neurons revealed that they provide the necessary input to cause increases in firing rate. Our results thus provide the first experimental evidence that feedback generates both neural and behavioral responses to low-contrast stimuli that are commonly found in the natural environment.

Stimulus background influences phase invariant coding by correlated neural activity.

Previously we reported that correlations between the activities of peripheral afferents mediate a phase invariant representation of natural communication stimuli that is refined across successive processing stages thereby leading to perception and behavior in the weakly electric fish Apteronotus leptorhynchus (Metzen et al., 2016). Here, we explore how phase invariant coding and perception of natural communication stimuli are affected by changes in the sinusoidal background over which they occur. We found that increasing background frequency led to phase locking, which decreased both detectability and phase invariant coding. Correlated afferent activity was a much better predictor of behavior as assessed from both invariance and detectability than single neuron activity. Thus, our results provide not only further evidence that correlated activity likely determines perception of natural communication signals, but also a novel explanation as to why these preferentially occur on top of low frequency as well as low-intensity sinusoidal backgrounds.

Electrosensory processing in Apteronotus albifrons: implications for general and specific neural coding strategies across wave-type weakly electric fish species.

Understanding how the brain processes sensory input to generate behavior remains an important problem in neuroscience. Towards this end, it is useful to compare results obtained across multiple species to gain understanding as to the general principles of neural coding. Here we investigated hindbrain pyramidal cell activity in the weakly electric fish Apteronotus albifrons We found strong heterogeneities when looking at baseline activity. Additionally, ON- and OFF-type cells responded to increases and decreases of sinusoidal and noise stimuli, respectively. While both cell types displayed band-pass tuning, OFF-type cells were more broadly tuned than their ON-type counterparts. The observed heterogeneities in baseline activity as well as the greater broadband tuning of OFF-type cells were both similar to those previously reported in other weakly electric fish species, suggesting that they constitute general features of sensory processing. However, we found that peak tuning occurred at frequencies ∼15 Hz in A. albifrons, which is much lower than values reported in the closely related species Apteronotus leptorhynchus and the more distantly related species Eigenmannia virescens In response to stimuli with time-varying amplitude (i.e., envelope), ON- and OFF-type cells displayed similar high-pass tuning curves characteristic of fractional differentiation and possibly indicate optimized coding. These tuning curves were qualitatively similar to those of pyramidal cells in the closely related species A. leptorhynchus In conclusion, comparison between our and previous results reveals general and species-specific neural coding strategies. We hypothesize that differences in coding strategies, when observed, result from different stimulus distributions in the natural/social environment.

Burst Firing in the Electrosensory System of Gymnotiform Weakly Electric Fish: Mechanisms and Functional Roles.

Neurons across sensory systems and organisms often display complex patterns of action potentials in response to sensory input. One example of such a pattern is the tendency of neurons to fire packets of action potentials (i.e., a burst) followed by quiescence. While it is well known that multiple mechanisms can generate bursts of action potentials at both the single-neuron and the network level, the functional role of burst firing in sensory processing is not so well understood to date. Here we provide a comprehensive review of the known mechanisms and functions of burst firing in processing of electrosensory stimuli in gymnotiform weakly electric fish. We also present new evidence from existing data showing that bursts and isolated spikes provide distinct information about stimulus variance. It is likely that these functional roles will be generally applicable to other systems and species.

Neural correlations enable invariant coding and perception of natural stimuli in weakly electric fish.

Neural representations of behaviorally relevant stimulus features displaying invariance with respect to different contexts are essential for perception. However, the mechanisms mediating their emergence and subsequent refinement remain poorly understood in general. Here, we demonstrate that correlated neural activity allows for the emergence of an invariant representation of natural communication stimuli that is further refined across successive stages of processing in the weakly electric fish Apteronotus leptorhynchus. Importantly, different patterns of input resulting from the same natural communication stimulus occurring in different contexts all gave rise to similar behavioral responses. Our results thus reveal how a generic neural circuit performs an elegant computation that mediates the emergence and refinement of an invariant neural representation of natural stimuli that most likely constitutes a neural correlate of perception.

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

Parallel sparse and dense information coding streams in the electrosensory midbrain.

Efficient processing of incoming sensory information is critical for an organism's survival. It has been widely observed across systems and species that the representation of sensory information changes across successive brain areas. Indeed, peripheral sensory neurons tend to respond densely to a broad range of sensory stimuli while more central neurons tend to instead respond sparsely to a narrow range of stimuli. Such a transition might be advantageous as sparse neural codes are thought to be metabolically efficient and optimize coding efficiency. Here we investigated whether the neural code transitions from dense to sparse within the midbrain Torus semicircularis (TS) of weakly electric fish. Confirming previous results, we found both dense and sparse coding neurons. However, subsequent histological classification revealed that most dense neurons projected to higher brain areas. Our results thus provide strong evidence against the hypothesis that the neural code transitions from dense to sparse in the electrosensory system. Rather, they support the alternative hypothesis that higher brain areas receive parallel streams of dense and sparse coded information from the electrosensory midbrain. We discuss the implications and possible advantages of such a coding strategy and argue that it is a general feature of sensory processing.

Coding stimulus amplitude by correlated neural activity.

While correlated activity is observed ubiquitously in the brain, its role in neural coding has remained controversial. Recent experimental results have demonstrated that correlated but not single-neuron activity can encode the detailed time course of the instantaneous amplitude (i.e., envelope) of a stimulus. These have furthermore demonstrated that such coding required and was optimal for a nonzero level of neural variability. However, a theoretical understanding of these results is still lacking. Here we provide a comprehensive theoretical framework explaining these experimental findings. Specifically, we use linear response theory to derive an expression relating the correlation coefficient to the instantaneous stimulus amplitude, which takes into account key single-neuron properties such as firing rate and variability as quantified by the coefficient of variation. The theoretical prediction was in excellent agreement with numerical simulations of various integrate-and-fire type neuron models for various parameter values. Further, we demonstrate a form of stochastic resonance as optimal coding of stimulus variance by correlated activity occurs for a nonzero value of noise intensity. Thus, our results provide a theoretical explanation of the phenomenon by which correlated but not single-neuron activity can code for stimulus amplitude and how key single-neuron properties such as firing rate and variability influence such coding. Correlation coding by correlated but not single-neuron activity is thus predicted to be a ubiquitous feature of sensory processing for neurons responding to weak input.

Coding of envelopes by correlated but not single-neuron activity requires neural variability.

Understanding how the brain processes sensory information is often complicated by the fact that neurons exhibit trial-to-trial variability in their responses to stimuli. Indeed, the role of variability in sensory coding is still highly debated. Here, we examined how variability influences neural responses to naturalistic stimuli consisting of a fast time-varying waveform (i.e., carrier or first order) whose amplitude (i.e., envelope or second order) varies more slowly. Recordings were made from fish electrosensory and monkey vestibular sensory neurons. In both systems, we show that correlated but not single-neuron activity can provide detailed information about second-order stimulus features. Using a simple mathematical model, we made the strong prediction that such correlation-based coding of envelopes requires neural variability. Strikingly, the performance of correlated activity at predicting the envelope was similarly optimally tuned to a nonzero level of variability in both systems, thereby confirming this prediction. Finally, we show that second-order sensory information can only be decoded if one takes into account joint statistics when combining neural activities. Our results thus show that correlated but not single-neural activity can transmit information about the envelope, that such transmission requires neural variability, and that this information can be decoded. We suggest that envelope coding by correlated activity is a general feature of sensory processing that will be found across species and systems.

Neural heterogeneities determine response characteristics to second-, but not first-order stimulus features.

Neural heterogeneities are seen ubiquitously, but how they determine neural response properties remains unclear. Here we show that heterogeneities can either strongly, or not at all, influence neural responses to a given stimulus feature. Specifically, we recorded from peripheral electroreceptor neurons, which display strong heterogeneities in their resting discharge activity, in response to naturalistic stimuli consisting of a fast time-varying waveform (i.e., first-order) whose amplitude (i.e., second-order or envelope) varied slowly in the weakly electric fish Apteronotus leptorhynchus. Although electroreceptors displayed relatively homogeneous responses to first-order stimulus features, further analysis revealed two subpopulations with similar sensitivities that were excited or inhibited by increases in the envelope, respectively, for stimuli whose frequency content spanned the natural range. We further found that a linear-nonlinear cascade model incorporating the known linear response characteristics to first-order features and a static nonlinearity accurately reproduced experimentally observed responses to both first- and second-order features for all stimuli tested. Importantly, this model correctly predicted that the response magnitude is independent of either the stimulus waveform's or the envelope's frequency content. Further analysis of our model led to the surprising prediction that the mean discharge activity can be used to determine whether a given neuron is excited or inhibited by increases in the envelope. This prediction was validated by our experimental data. Thus, our results provide key insight as to how neural heterogeneities can determine response characteristics to some, but not other, behaviorally relevant stimulus features.

Weakly electric fish display behavioral responses to envelopes naturally occurring during movement: implications for neural processing.

How the brain processes natural sensory input remains an important and poorly understood problem in neuroscience. The efficient coding hypothesis asserts that the brain's coding strategies are adapted to the statistics of natural stimuli in order to efficiently process them, thereby optimizing their perception by the organism. Here we examined whether gymnotiform weakly electric fish displayed behavioral responses that are adapted to the statistics of the natural electrosensory envelopes. Previous studies have shown that the envelopes resulting from movement tend to consist of low (<1 Hz) temporal frequencies and are behaviorally relevant whereas those resulting from social interactions consist of higher (>1 Hz) temporal frequencies that can thus mask more behaviorally relevant signals. We found that the self-generated electric organ discharge frequency follows the detailed time course of the envelope around a mean value that is positively offset with respect to its baseline value for temporal frequencies between 0.001 Hz and 1 Hz. The frequency-following component of this behavioral response decreased in magnitude as a power law as a function of the envelope frequency and was negligible for envelope frequencies above 1 Hz. In contrast, the offset component was relatively constant and somewhat increased for envelope frequencies above 1 Hz. Thus, our results show that weakly electric fish display behavioral responses that track the detailed time course of low but not high frequency envelope stimuli. Furthermore, we found that the magnitude of the frequency-following behavioral response matches, in a one-to-one fashion, the spectral power of natural second-order stimulus attributes observed during movement. Indeed, both decayed as a power law with the same exponent for temporal frequencies spanning three orders of magnitude. Thus, our findings suggest that the neural coding strategies used by weakly electric fish perceive the detailed time course of movement envelopes and are adapted to their statistics as found in the natural environment. They also suggest that weakly electric fish might take advantage of the differential frequency content of movement and social envelopes in order to give appropriate behavioral responses during encounters between two or more conspecifics.

Serotonin selectively enhances perception and sensory neural responses to stimuli generated by same-sex conspecifics.

Centrifugal serotonergic fibers innervating sensory brain areas are seen ubiquitously across systems and species but their function remains unclear. Here we examined the functional role of serotonergic innervation onto electrosensory neurons in weakly electric fish by eliciting endogenous release through electrical stimulation as well as exogenous focal application of serotonin in the vicinity of the cell being recorded from. Both approaches showed that the function of serotonergic input onto electrosensory pyramidal neurons is to render them more excitable by reducing the spike afterhyperpolarization amplitude and thereby promoting burst firing. Further, serotonergic input selectively improved neuronal responses to stimuli that occur during interactions between same-sex conspecifics but not to stimuli associated with either prey or that occur during interactions between opposite-sex conspecifics. Finally, we tested whether serotonin-mediated enhanced pyramidal neuron responses to stimuli associated with same-sex conspecifics actually increase perception by the animal. Our behavioral experiments show that exogenous injection and endogenous release of serotonin both increase the magnitude of behavioral responses to stimuli associated with same-sex conspecifics as well as simultaneously decrease aggressive behaviors. Thus, our data indicate that the serotonergic system inhibits aggressive behavior toward same-sex conspecifics, while at the same time increasing perception of stimuli associated with these individuals. This function is likely to be conserved across systems and species.

Descending projections to the hindbrain and spinal cord in the paddlefish Polyodon spathula.

In vertebrates, almost all motor neurons innervating skeletal muscles are located in the hindbrain and spinal cord, and all brain centers that control behavior have descending projections into these parts of the central nervous system. With tracer injections into the spinal cord and hindbrain, we have studied cell groups with descending projections in the paddlefish. Spinal cord injections reveal retrogradely labeled cells in all reticular and raphe nuclei, as well as the nucleus of the medial longitudinal fascicle. Additional cell groups with projections to the spinal cord are the nucleus of the fasciculus solitarius, descending trigeminal nucleus, several octavolateral nuclei, the dorsal hypothalamic nucleus, and the pretectum. The only primary sensory fibers with descending projections are trigeminal fibers. Hindbrain injections reveal a number of additional cell groups in di- and mesencephalon. The most prominent source is the mesencephalic tectum. Other descending cells were found in the dorsal posterior thalamic nucleus, ventral thalamus, torus semicircularis, lateral mesencephalic nucleus, and the central gray of the mesencephalon. Our data show that descending spinal projections are comparable to those of other vertebrates and that the tectum is the most important motor control center projecting to the hindbrain. A surprising result was that the dorsal posterior thalamic nucleus also projects to the hindbrain. This nucleus is thought to be a center that relays sensory information to the telencephalon. Further studies are needed to determine the complete set of projections of the dorsal thalamus in paddlefish and other fishes to gain insights into its functional role.