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Many theories of brain function propose that activity in sparse subsets of neurons underlies perception and action. To place a lower bound on the amount of neural activity that can be perceived, we used an all-optical approach to drive behaviour with targeted two-photon optogenetic activation of small ensembles of L2/3 pyramidal neurons in mouse barrel cortex while simultaneously recording local network activity with two-photon calcium imaging. By precisely titrating the number of neurons stimulated, we demonstrate that the lower bound for perception of cortical activity is ~14 pyramidal neurons. We find a steep sigmoidal relationship between the number of activated neurons and behaviour, saturating at only ~37 neurons, and show this relationship can shift with learning. Furthermore, activation of ensembles is balanced by inhibition of neighbouring neurons. This surprising perceptual sensitivity in the face of potent network suppression supports the sparse coding hypothesis, and suggests that cortical perception balances a trade-off between minimizing the impact of noise while efficiently detecting relevant signals.

We have previously reported that central neurons mediating vestibulo-spinal reflexes and self-motion perception optimally encode natural self-motion (Mitchell et al., 2018). Importantly however, the vestibular nuclei also comprise other neuronal classes that mediate essential functions such as the vestibulo-ocular reflex (VOR) and its adaptation. Here we show that heterogeneities in resting discharge variability mediate a trade-off between faithful encoding and optimal coding via temporal whitening. Specifically, neurons displaying lower variability did not whiten naturalistic self-motion but instead faithfully represented the stimulus’ detailed time course, while neurons displaying higher variability displayed temporal whitening. Using a well-established model of VOR pathways, we demonstrate that faithful stimulus encoding is necessary to generate the compensatory eye movements found experimentally during naturalistic self-motion. Our findings suggest a novel functional role for variability toward establishing different coding strategies: (1) faithful stimulus encoding for generating the VOR; (2) optimized coding via temporal whitening for other vestibular functions.

Optimal decision-making requires that stimulus-value associations are kept up to date by constantly comparing the expected value of a stimulus with its experienced outcome. To do this, value information must be held in mind when a stimulus and outcome are separated in time. However, little is known about the neural mechanisms of working memory (WM) for value. Contradicting theories have suggested WM requires either persistent or transient neuronal activity, with stable or dynamic representations, respectively. To test these hypotheses, we recorded neuronal activity in the orbitofrontal and anterior cingulate cortex of two monkeys performing a valuation task. We found that features of all hypotheses were simultaneously present in prefrontal activity, and no single hypothesis was exclusively supported. Instead, mixed dynamics supported robust, time invariant value representations while also encoding the information in a temporally specific manner. We suggest that this hybrid coding is a critical mechanism supporting flexible cognitive abilities.

Over days and weeks, neural activity representing an animal’s position and movement in sensorimotor cortex has been found to continually reconfigure or ‘drift’ during repeated trials of learned tasks, with no obvious change in behavior. This challenges classical theories, which assume stable engrams underlie stable behavior. However, it is not known whether this drift occurs systematically, allowing downstream circuits to extract consistent information. Analyzing long-term calcium imaging recordings from posterior parietal cortex in mice (Mus musculus), we show that drift is systematically constrained far above chance, facilitating a linear weighted readout of behavioral variables. However, a significant component of drift continually degrades a fixed readout, implying that drift is not confined to a null coding space. We calculate the amount of plasticity required to compensate drift independently of any learning rule, and find that this is within physiologically achievable bounds. We demonstrate that a simple, biologically plausible local learning rule can achieve these bounds, accurately decoding behavior over many days.

Purkinje neurons (PN) in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from electrical engineering, particularly signal processing and digital/analog circuits. By viewing the PN as an unknown circuit to be reverse-engineered, we can use the tools that provide the foundations of today's integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the PN and define three unique frequency ranges associated with the cells' output. Comparing the PN to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the PN can act as a multivibrator circuit.

Purkinje neurons (PN) in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from electrical engineering, particularly signal processing and digital/analog circuits. By viewing the PN as an unknown circuit to be reverse-engineered, we can use the tools that provide the foundations of todays integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the PN and define three unique frequency ranges associated with the cells output. Comparing the PN to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the PN can act as a multivibrator circuit.

Current neural prostheses can restore limb movement to tetraplegic patients by translating brain signals coding movements to control a variety of actuators. Fast and accurate somatosensory feedback is essential for normal movement, particularly dexterous tasks, but is currently lacking in motor neural prostheses. Attempts to restore somatosensory feedback have largely focused on cortical stimulation which, thus far, have succeeded in eliciting minimal naturalistic sensations. Yet, a question that deserves more attention is whether the cortex is the best place to activate the central nervous system to restore somatosensation. Here, we propose that the brainstem dorsal column nuclei are an ideal alternative target to restore somatosensation. We review some of the recent literature investigating the dorsal column nuclei functional organization and neurophysiology and highlight some of the advantages and limitations of the dorsal column nuclei as a future neural prosthetic target. Recent evidence supports the dorsal column nuclei as a potential neural prosthetic target, but also identifies several gaps in our knowledge as well as potential limitations which need to be addressed before such a goal can become reality.

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).

Speech evokes robust activity in auditory cortex, which contains information over a wide range of spatial and temporal scales. It remains unclear which components of these neural representations are causally involved in the perception and processing of speech sounds. Here we compared the relative importance of early and late speech-evoked activity for consonant discrimination. We trained mice to discriminate the initial consonants in spoken words, and then tested the effect of optogenetically suppressing different temporal windows of speech-evoked activity in auditory cortex. We found that both early and late suppression disrupted performance equivalently. These results suggest that mice are impaired at recognizing either type of disrupted representation because it differs from those learned in training.

Christianne E Strang, Mary Katherine Ray, Mary M Boggiano, Franklin R Amthor Department of Psychology, The University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Transcranial direct current stimulation (tDCS) has been studied in humans for its effects on enhancement of learning, amelioration of psychiatric disorders, and modification of other behaviors for over 50 years. Typical treatments involve injecting 2 mA current through scalp electrodes for 20 minutes, sometimes repeated weekly for two to five sessions. Little is known about the direct effects of tDCS at the neural circuit or the cellular level. This study assessed the effects of tDCS-like currents on the central nervous system by recording effects on retinal ganglion cell responsiveness using the rabbit retina eyecup preparation. Materials and methods: We examined changes in firing to On and Off light stimuli during and after brief applications of a range of currents and polarity and in different classes of ganglion cells. Results: The responses of Sustained cells were consistently suppressed during the first round of current application, but responses could be enhanced after subsequent rounds of stimulation. The observed first round suppression was independent of current polarity, amplitude, or number of trials. However, the light responses of Transient cells were more likely to be enhanced by negative currents and unaffected or suppressed by first round positive currents. Short-duration currents, that is, minutes, as low as 2.5 µA produced a remarkable persistency of firing changes, for up to 1.5 hours, after cessation of current. Conclusion: The results are consistent with postulated tDCS alteration of central nervous system function, which outlast the tDCS session and provide evidence for the isolated retina as a useful model to understand tDCS actions at the neuronal level. Keywords: tDCS mechanisms, CNS, in vitro model, neural coding, neuromodulation

A ten-layer feed forward network was constructed in the presence of an exogenous alternating magnetic field. Results indicate that for rate coding, the firing rate is increased in the presence of an exogenous alternating magnetic field and particularly with increasing enhancement of the alternating magnetic field amplitude. For temporal coding, in the presence of alternating magnetic field, the interspike intervals of the spiking sequence are decreased and the distribution of interspike intervals tends to be uniform.

Complex behaviors are often driven by an internal model, which integrates sensory information over time and facilitates long-term planning to reach subjective goals. A fundamental challenge in neuroscience is, How can we use behavior and neural activity to understand this internal model and its dynamic latent variables? Here we interpret behavioral data by assuming an agent behaves rationally--that is, it takes actions that optimize its subjective reward according to its understanding of the task and its relevant causal variables. We apply a method, inverse rational control (IRC), to learn an agent's internal model and reward function by maximizing the likelihood of its measured sensory observations and actions. This thereby extracts rational and interpretable thoughts of the agent from its behavior. We also provide a framework for interpreting encoding, recoding, and decoding of neural data in light of this rational model for behavior. When applied to behavioral and neural data from simulated agents performing suboptimally on a naturalistic foraging task, this method successfully recovers their internal model and reward function, as well as the Markovian computational dynamics within the neural manifold that represent the task. This work lays a foundation for discovering how the brain represents and computes with dynamic latent variables. [ABSTRACT FROM AUTHOR]

How does organized cognition arise from distributed brain activity? Recent analyses of fluid intelligence suggest a core process of cognitive focus and integration, organizing the components of a cognitive operation into the required computational structure. A cortical 'multiple-demand' (MD) system is closely linked to fluid intelligence, and recent imaging data define nine specific MD patches distributed across frontal, parietal, and occipitotemporal cortex. Wide cortical distribution, relative functional specialization, and strong connectivity suggest a basis for cognitive integration, matching electrophysiological evidence for binding of cognitive operations to their contents. Though still only in broad outline, these data suggest how distributed brain activity can build complex, organized cognition. Fluid intelligence tests predict success in many activities, suggesting cognitive mechanisms of broad importance. We propose a core process of attentional integration. Complex problems must be segmented into simpler parts. Attention to each part integrates cognitive fragments into a computational structure. Fluid intelligence is linked to the brain's multiple-demand (MD) system, defined by common activity across different cognitive demands. Across the brain, MD patches shows anatomical and physiological properties adapted to attentional integration. Neurophysiology of putative MD regions shows adaptive coding of task-relevant information. Suiting attentional integration, many neurons show conjunctive coding (e.g., binding cognitive operations to their target objects). In broad outline, these results suggest how distributed brain activity builds organized cognition. [ABSTRACT FROM AUTHOR]

Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re‐connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus‐mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi‐channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin‐film light‐emitting diodes (μLEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of μLED‐based oCIs for spectrally selective activation of the auditory nerve. Synopsis: Electrical cochlear implants effectiveness in individuals remains limited by the spread of the electric current in the cochlea. This study explores the potential of optogenetics for hearing restoration through combining optogenetic manipulation of the auditory nerve with microsystems engineering. μLED‐based optical cochlear implants (oCI) enable stimulation of the rodent auditory nerve.The strength of induced responses scales with the number of recruited emitters.μLED‐evoked neural responses are tonotopic and spectrally selective.The combination of gene therapy and microsystems engineering enables optical activation of the auditory nerve with higher spectral precision in gerbils. [ABSTRACT FROM AUTHOR]

The encoding of information in spike phase relative to local field potential (LFP) oscillations offers several theoretical advantages over equivalent firing rate codes. One notable example is provided by place and grid cells in the rodent hippocampal formation, which exhibit phase precession—firing at progressively earlier phases of the 6–12 Hz movement‐related theta rhythm as their spatial firing fields are traversed. It is often assumed that such phase coding relies on a high amplitude baseline oscillation with relatively constant frequency. However, sustained oscillations with fixed frequency are generally absent in LFP and spike train recordings from the human brain. Hence, we examine phase coding relative to LFP signals with broadband low‐frequency (2–20 Hz) power but without regular rhythmicity. We simulate a population of grid cells that exhibit phase precession against a baseline oscillation recorded from depth electrodes in human hippocampus. We show that this allows grid cell firing patterns to multiplex information about location, running speed and movement direction, alongside an arbitrary fourth variable encoded in LFP frequency. This is of particular importance given recent demonstrations that movement direction, which is essential for path integration, cannot be recovered from head direction cell firing rates. In addition, we investigate how firing phase might reduce errors in decoded location, including those arising from differences in firing rate across grid fields. Finally, we describe analytical methods that can identify phase coding in the absence of high amplitude LFP oscillations with approximately constant frequency, as in single unit recordings from the human brain and consistent with recent data from the flying bat. We note that these methods could also be used to detect phase coding outside of the spatial domain, and that multi‐unit activity can substitute for the LFP signal. In summary, we demonstrate that the computational advantages offered by phase coding are not contingent on, and can be detected without, regular rhythmicity in neural activity. [ABSTRACT FROM AUTHOR]

Olfaction is fundamentally distinct from other sensory modalities. Natural odor stimuli are complex mixtures of volatile chemicals that interact in the nose with a receptor array that, in rodents, is built from more than 1,000 unique receptors. These interactions dictate a peripheral olfactory code, which in the brain is transformed and reformatted as it is broadcast across a set of highly interconnected olfactory regions. Here we discuss the problems of characterizing peripheral population codes for olfactory stimuli, of inferring the specific functions of different higher olfactory areas given their extensive recurrence, and of ultimately understanding how odor representations are linked to perception and action. We argue that, despite the differences between olfaction and other sensory modalities, addressing these specific questions will reveal general principles underlying brain function. [ABSTRACT FROM AUTHOR]

The temporal pattern of action potentials can convey rich information in a variety of sensory systems. We describe a new non-invasive technique that enables precise, reliable generation of action potential patterns in tactile peripheral afferent neurons by brief taps on the skin. Using this technique, we demonstrate sophisticated coding of temporal information in the somatosensory system, that shows that perceived vibration frequency is not encoded in peripheral afferents as was expected by either their firing rate or the underlying periodicity of the stimulus. Instead, a burst gap or silent gap between trains of action potentials conveys frequency information. This opens the possibility of new encoding strategies that could be deployed to convey sensory information using mechanical or electrical stimulation in neural prostheses and brain-machine interfaces, and may extend to senses beyond artificial encoding of aspects of touch. We argue that a focus on appropriate use of effective temporal coding offers more prospects for rapid improvement in the function of these interfaces than attempts to scale-up existing devices. [ABSTRACT FROM AUTHOR]

Neural coding is a key problem in neuroscience aimed to understand the information processing mechanism in brain. Among the classical theories of neural coding, population rate coding has been studied widely in many works. In computational studies, neurons are usually classified into excitatory or inhibitory ones. Excitatory neurons have excitatory output synapses, and inhibitory neurons have inhibitory output synapses. However, according to physiological observations, neurons potentially have both types of output synapses. Thus, in this paper, neuronal networks consisting of neurons with mixed excitatory–inhibitory synapses are constructed to investigate the population rate coding fidelity of neuronal systems. It is revealed that, under intermediate values of recurrent probability, inhibitory–excitatory strength ratio, and noise intensity, the performance of population rate coding could be improved by both excitatory synaptic strength and synaptic time constant. It is indicated that external stimuli can be encoded in the form of population firing rate by the studied neuronal networks very well. What is more exciting is that we find the neuronal networks considered in our work have higher coding efficiency than the traditional ones. Therefore, neurons with mixed excitatory–inhibitory synapses may be much more rational. [ABSTRACT FROM AUTHOR]

Key points: We measured fractal (self‐similar) fluctuations in ongoing spiking activity in subcortical (lateral geniculate nucleus, LGN) and cortical (area MT) visual areas in anaesthetised marmosets.Cells in the evolutionary ancient koniocellular LGN pathway and in area MT show high‐amplitude fractal fluctuations, whereas evolutionarily newer parvocellular and magnocellular LGN cells do not.Spiking activity in koniocellular cells and MT cells shows substantial correlation to the local population activity, whereas activity in parvocellular and magnocellular cells is less correlated with local activity.We develop a model consisting of a fractal process and a global rate modulation which can reproduce and explain the fundamental relationship between fractal fluctuations and population coupling in LGN and MT.The model provides a unified account of apparently disparate aspects of neural spiking activity and can improve our understanding of information processing in evolutionary ancient and modern visual pathways. The brain represents and processes information through patterns of spiking activity, which is influenced by local and widescale brain circuits as well as intrinsic neural dynamics. Whether these influences have independent or linked effects on spiking activity is, however, not known. Here we measured spiking activity in two visual centres, the lateral geniculate nucleus (LGN) and cortical area MT, in marmoset monkeys. By combining the Fano‐factor time curve, power spectral analysis and rescaled range analysis, we reveal inherent fractal fluctuations of spiking activity in LGN and MT. We found that the evolutionary ancient koniocellular (K) pathway in LGN and area MT exhibits strong fractal fluctuations at short (<1 s) time scales. Parvocellular (P) and magnocellular (M) LGN cells show weaker fractal fluctuations at longer (multi‐second) time scales. In both LGN and MT, the amplitude and time scale of fractal fluctuations can explain short and long time scale spiking dynamics. We further show differential neuronal coupling of LGN and MT cells to local population spiking activity. The population coupling is intrinsically linked to fractal fluctuations: neurons showing stronger fluctuations are more strongly correlated to the local population activity. To understand this relationship, we modelled spiking activity using a fractal inhomogeneous Poisson process with dynamic rate, which is the product of an intrinsic stochastic fractal rate and a global modulatory gain. Our model explains the intrinsic links between neuronal spike rate and population coupling in LGN and MT, and establishes a unified account of dynamic spiking properties in afferent visual pathways. Key points: We measured fractal (self‐similar) fluctuations in ongoing spiking activity in subcortical (lateral geniculate nucleus, LGN) and cortical (area MT) visual areas in anaesthetised marmosets.Cells in the evolutionary ancient koniocellular LGN pathway and in area MT show high‐amplitude fractal fluctuations, whereas evolutionarily newer parvocellular and magnocellular LGN cells do not.Spiking activity in koniocellular cells and MT cells shows substantial correlation to the local population activity, whereas activity in parvocellular and magnocellular cells is less correlated with local activity.We develop a model consisting of a fractal process and a global rate modulation which can reproduce and explain the fundamental relationship between fractal fluctuations and population coupling in LGN and MT.The model provides a unified account of apparently disparate aspects of neural spiking activity and can improve our understanding of information processing in evolutionary ancient and modern visual pathways. [ABSTRACT FROM AUTHOR]

Key points: The function of serotonergic fibres onto sensory areas remains poorly understoodWe show that serotonin application enhances sensory neural and behavioural responses to second order stimuliEnhanced neural responses most likely occurred because of increased burst firingChanges in neural sensitivity due to burst firing were the best predictor of changes in behavioural sensitivityOur results suggest that serotonin optimizes coding of stimuli encountered during aggression. Understanding how the processing of sensory information leads to behavioural responses remains a central problem in systems neuroscience. Here, we investigated how the neuromodulator serotonin affects neural and behavioural responses to second‐order envelope stimuli within the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We found that serotonin application increased neuronal excitability through greater tendency for burst firing. We found that increased excitability led to overall higher neural sensitivities to higher envelope frequencies. Separating the spike train into bursts and isolated spike train components revealed that this was due to significant increases in neural sensitivity for the former but not the latter. We next investigated the consequences of such changes in sensitivity towards optimized coding of stimuli with specific statistics. Our results show that serotonin application compromised optimal coding of stimuli with statistics seen under naturalistic conditions due to changes in burst, but not isolated spike firing. Finally, we found that serotonin application increased behavioural sensitivity to envelope stimuli. Interestingly, changes in neural sensitivity due to bursts were a far better predictor of changes in behavioural sensitivity, suggesting that burst firing is decoded by downstream brain areas. Overall, our results suggest that serotonin modulates neural responses to optimize coding and perception of stimuli during behavioural contexts associated with encountering dominant conspecifics. Key points: The function of serotonergic fibres onto sensory areas remains poorly understoodWe show that serotonin application enhances sensory neural and behavioural responses to second order stimuliEnhanced neural responses most likely occurred because of increased burst firingChanges in neural sensitivity due to burst firing were the best predictor of changes in behavioural sensitivityOur results suggest that serotonin optimizes coding of stimuli encountered during aggression. [ABSTRACT FROM AUTHOR]

In this research, we develop a neuromorphic system to study neural signaling at the level of first order tactile afferents which are slowly adapting type I (SA1) and rapidly adapting type I (RA1) mechanoreceptors. Considering, the linearized Izhikevich model, two digital circuits are developed for both afferents and are executed on the field programmable gate array (FPGA). After implementation of the digital circuits, we investigate how much information is encoded by this hardware-based neuromorphic system. Indeed, the artificial spiking sequences are evoked by applying different force profiles to the sensor connected to the FPGA. Next, the obtained neural responses are classified based on the two fundamental neural coding for brain information processing: spike timing and rate coding. Considering temporal coding, k-nearest neighbors (kNN), support vector machine (SVM) and Decision Tree algorithms are used for forces recognition using acquired artificial spike patterns. The results of classification show that the digital RA1 is susceptible to signal variations, while the digital SA1, on the other hand, is sensitive to the ramp and hold inputs. Furthermore, these responses are better distinguishable to different stimuli when both artificial SA1 and RA1 afferents are regarded. These results, which are functionally compatible with biological observations, yield the promise for fabrication and development of new tactile sensing modules to be employed in bio-robotic and prosthetic applications. [ABSTRACT FROM AUTHOR]

Current neural prostheses can restore limb movement to tetraplegic patients by translating brain signals coding movements to control a variety of actuators. Fast and accurate somatosensory feedback is essential for normal movement, particularly dexterous tasks, but is currently lacking in motor neural prostheses. Attempts to restore somatosensory feedback have largely focused on cortical stimulation which, thus far, have succeeded in eliciting minimal naturalistic sensations. Yet, a question that deserves more attention is whether the cortex is the best place to activate the central nervous system to restore somatosensation. Here, we propose that the brainstem dorsal column nuclei are an ideal alternative target to restore somatosensation. We review some of the recent literature investigating the dorsal column nuclei functional organization and neurophysiology and highlight some of the advantages and limitations of the dorsal column nuclei as a future neural prosthetic target. Recent evidence supports the dorsal column nuclei as a potential neural prosthetic target, but also identifies several gaps in our knowledge as well as potential limitations which need to be addressed before such a goal can become reality. [ABSTRACT FROM AUTHOR]

Understanding the neural code requires understanding how populations of neurons code information. Theoretical models predict that information may be limited by correlated noise in large neural populations. Nevertheless, analyses based on tens of neurons have failed to find evidence of saturation. Moreover, some studies have shown that noise correlations can be very small, and therefore may not affect information coding. To determine whether information-limiting correlations exist, we implanted eight Utah arrays in prefrontal cortex (PFC; area 46) of two male macaque monkeys, recording >500 neurons simultaneously. We estimated information in PFC about saccades as a function of ensemble size. Noise correlations were, on average, small (~10 -3). However, information scaled strongly sublinearly with ensemble size. After shuffling trials, destroying noise correlations, information was a linear function of ensemble size. Thus, we provide evidence for the existence of information-limiting noise correlations in large populations of PFC neurons. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Speech evokes robust activity in auditory cortex, which contains information over a wide range of spatial and temporal scales. It remains unclear which components of these neural representations are causally involved in the perception and processing of speech sounds. Here we compared the relative importance of early and late speech-evoked activity for consonant discrimination. We trained mice to discriminate the initial consonants in spoken words, and then tested the effect of optogenetically suppressing different temporal windows of speech-evoked activity in auditory cortex. We found that both early and late suppression disrupted performance equivalently. These results suggest that mice are impaired at recognizing either type of disrupted representation because it differs from those learned in training. [ABSTRACT FROM AUTHOR]

Machine learning is yielding unprecedented interest in research and industry, due to recent success in many applied contexts such as image classification and object recognition. However, the deployment of these systems requires huge computing capabilities, thus making them unsuitable for embedded systems. To deal with this limitation, many researchers are investigating brain-inspired computing, which would be a perfect alternative to the conventional Von Neumann architecture based computers (CPU/GPU) that meet the requirements for computing performance, but not for energy-efficiency. Therefore, neuromorphic hardware circuits that are adaptable for both parallel and distributed computations need to be designed. In this paper, we focus on Spiking Neural Networks (SNNs) with a comprehensive study of neural coding methods and hardware exploration. In this context, we propose a framework for neuromorphic hardware design space exploration, which allows to define a suitable architecture based on application-specific constraints and starting from a wide variety of possible architectural choices. For this framework, we have developed a behavioral level simulator for neuromorphic hardware architectural exploration named NAXT. Moreover, we propose modified versions of the standard Rate Coding technique to make trade-offs with the Time Coding paradigm, which is characterized by the low number of spikes propagating in the network. Thus, we are able to reduce the number of spikes while keeping the same neuron's model, which results in an SNN with fewer events to process. By doing so, we seek to reduce the amount of power consumed by the hardware. Furthermore, we present three neuromorphic hardware architectures in order to quantitatively study the implementation of SNNs. One of these architectures integrates a novel hybrid structure: a highly-parallel computation core for most solicited layers, and time-multiplexed computation units for deeper layers. These architectures are derived from a novel funnel-like Design Space Exploration framework for neuromorphic hardware. [ABSTRACT FROM AUTHOR]

• Spatial memories remains stable despite dramatic changes in running speed. • Neuronal firing rates and temporal dynamics are both altered by running speed. • Speed-dependent neural codes may help stabilize spatial memories. • Speed codes altered by stimulation of medial septum and brainstem locomotor regions. • Critical to identify which region provides the earliest prediction of speed change. Ants who have successfully navigated the long distance between their foraging spot and their nest dozens of times will drastically overshoot their destination if the size of their legs is doubled by the addition of stilts. This observation reflects a navigational strategy called path integration, a strategy also utilized by mammals. Path integration necessitates that animals keep track of their movement speed and use it to precisely and instantly modify where they think they are and where they want to go. Here we review the neural circuitry that has evolved to integrate speed and space. We start with the rate and temporal codes for speed in the hippocampus and work backwards towards the motor and sensory systems. We highlight the need for experiments designed to differentiate the respective contributions of motor efference copy versus sensory inputs. In particular, we discuss the importance of high-resolution tracking of the latency of speed-encoding as a precise way to disentangle the sensory versus motor computations that enable successful spatial navigation at very different speeds. [ABSTRACT FROM AUTHOR]

Sensory systems encounter remarkably diverse stimuli in the external environment. Natural stimuli exhibit timescales and amplitudes of variation that span a wide range. Mechanisms of adaptation, a ubiquitous feature of sensory systems, allow for the accommodation of this range of scales. Are there common rules of adaptation across different sensory modalities? We measured the membrane potential responses of individual neurons in the visual, somatosensory, and auditory cortices of male and female mice to discrete, punctate stimuli delivered at a wide range of fixed and nonfixed frequencies. We find that the adaptive profile of the response is largely preserved across these three areas, exhibiting attenuation and responses to the cessation of stimulation, which are signatures of response to changes in stimulus statistics. We demonstrate that these adaptive responses can emerge from a simple model based on the integration of fixed filters operating over multiple time scales. [ABSTRACT FROM AUTHOR]

A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods.

We propose a simple measure of neural sensitivity for characterizing stimulus coding. Sensitivity is defined as the fraction of neurons that show positive responses to n stimuli out of a total of N. To determine a positive response, we propose two methods: Fisherian statistical testing and a data-driven Bayesian approach to determine the response probability of a neuron. The latter is non-parametric, data-driven, and captures a lower bound for the probability of neural responses to sensory stimulation. Both methods are compared with a standard test that assumes normal probability distributions. We applied the sensitivity estimation based on the proposed method to experimental data recorded from the mushroom body (MB) of locusts. We show that there is a broad range of sensitivity that the MB response sweeps during odor stimulation. The neurons are initially tuned to specific odors, but tend to demonstrate a generalist behavior towards the end of the stimulus period, meaning that the emphasis shifts from discrimination to feature learning.

Synapses preferentially respond to particular temporal patterns of activity with a large degree of heterogeneity that is informally or tacitly separated into classes. Yet, the precise number and properties of such classes are unclear. Do they exist on a continuum and, if so, when is it appropriate to divide that continuum into functional regions? In a large dataset of glutamatergic cortical connections, we perform model-based characterization to infer the number and characteristics of functionally distinct subtypes of synaptic dynamics. In rodent data, we find five clusters that partially converge with transgenic-associated subtypes. Strikingly, the application of the same clustering method in human data infers a highly similar number of clusters, supportive of stable clustering. This nuanced dictionary of functional subtypes shapes the heterogeneity of cortical synaptic dynamics and provides a lens into the basic motifs of information transmission in the brain. [Display omitted] • Excitatory synaptic dynamics in cortex exist in distinct groups rather than on a continuum • Organization of cortical synaptic dynamics is more nuanced than facilitation and depression • Cell-type-specific differences are more resolvable at physiological calcium concentration • Subtypes partially align with transgenically defined subclasses Beninger et al. combine synaptic modeling and machine learning to infer the number and the characteristics of functional subtypes of cortical synaptic dynamics in humans and mice. These subtypes cannot be accounted for by continuum hypotheses, are similar between species, and partly overlap transgenic-associated types. [ABSTRACT FROM AUTHOR]

High-frequency “burst” clusters of spikes are a generic output pattern of many neurons. While bursting is a ubiquitous computational feature of different nervous systems across animal species, the encoding of synaptic inputs by bursts is not well understood. We find that bursting neurons in the rodent thalamus employ “multiplexing” to differentially encode low- and high-frequency stimulus features associated with either T-type calcium “low-threshold” or fast sodium spiking events, respectively, and these events adapt differently. Thus, thalamic bursts encode disparate information in three channels: (1) burst size, (2) burst onset time, and (3) precise spike timing within bursts. Strikingly, this latter “intraburst” encoding channel shows millisecond-level feature selectivity and adapts across statistical contexts to maintain stable information encoded per spike. Consequently, calcium events both encode low-frequency stimuli and, in parallel, gate a transient window for high-frequency, adaptive stimulus encoding by sodium spike timing, allowing bursts to efficiently convey fine-scale temporal information.

Human sound localization is an important computation performed by the brain. Models of sound localization commonly assume that sound lateralization from interaural time differences is level invariant. Here we observe that two prevalent theories of sound localization make opposing predictions. The labelled-line model encodes location through tuned representations of spatial location and predicts that perceived direction is level invariant. In contrast, the hemispheric-difference model encodes location through spike-rate and predicts that perceived direction becomes medially biased at low sound levels. Here, behavioral experiments find that softer sounds are perceived closer to midline than louder sounds, favoring rate-coding models of human sound localization. Analogously, visual depth perception, which is based on interocular disparity, depends on the contrast of the target. The similar results in hearing and vision suggest that the brain may use a canonical computation of location: encoding perceived location through population spike rate relative to baseline.

Environmental signals act as input and are processed across successive stages in the brain to generate a meaningful behavioral output. However, a ubiquitous observation is that descending feedback projections from more central to more peripheral brain areas vastly outnumber ascending feedforward projections. Such projections generally act to modify how sensory neurons respond to afferent signals. Recent studies in the electrosensory system of weakly electric fish have revealed novel functions for feedback pathways in that their transformation of the afferent input generates neural firing rate responses to sensory signals mediating perception and behavior. In this review, we focus on summarizing these novel and recently uncovered functions and put them into context by describing the more “classical” functions of feedback in the electrosensory system. We further highlight the parallels between the electrosensory system and other systems as well as outline interesting future directions.

Properties of synaptic release dictates the core of information transfer in neural circuits. Despite decades of technical and theoretical advances, distinguishing bona fide information content from the multiple sources of synaptic variability remains a challenging problem. Here, we employed a combination of computational approaches with cellular electrophysiology, two-photon uncaging of MNI-Glutamate and imaging at single synapses. We describe and calibrate the use of the fluorescent glutamate sensor iGluSnFR and found that its kinetic profile is close to that of AMPA receptors, therefore providing several distinct advantages over slower methods relying on NMDA receptor activation (i.e., chemical or genetically encoded calcium indicators). Using an array of statistical methods, we further developed, and validated on surrogate data, an expectation-maximization algorithm that, by biophysically constraining release variability, extracts the quantal parameters n (maximum number of released vesicles) and p (unitary probability of release) from single-synapse iGluSnFR-mediated transients. Together, we present a generalizable mathematical formalism which, when applied to optical recordings, paves the way to an increasingly precise investigation of information transfer at central synapses.

Grid cells in the medial entorhinal cortex (MEC) encode position using a distributed representation across multiple neural populations (modules), each possessing a distinct spatial scale. The modular structure of the representation confers the grid cell neural code with large capacity. Yet, the modularity poses significant challenges for the neural circuitry that maintains the representation, and updates it based on self motion. Small incompatible drifts in different modules, driven by noise, can rapidly lead to large, abrupt shifts in the represented position, resulting in catastrophic readout errors. Here, we propose a theoretical model of coupled modules. The coupling suppresses incompatible drifts, allowing for a stable embedding of a two-dimensional variable (position) in a higher dimensional neural attractor, while preserving the large capacity. We propose that coupling of this type may be implemented by recurrent synaptic connectivity within the MEC with a relatively simple and biologically plausible structure.