Contributions of cortical neuron firing patterns, synaptic connectivity, and plasticity to task performance.

Neuronal responses during behavior are diverse, ranging from highly reliable 'classical' responses to irregular 'non-classically responsive' firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity. Reliable and irregular units contribute differentially to task performance via output and recurrent connections, respectively. Excitatory plasticity shifts the response distribution while inhibition constrains its diversity. Together both improve task performance with full network engagement. The same local patterns of synaptic inputs predict spiking response properties of network units and auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus, diverse neural responses contribute to network function and emerge from synaptic plasticity rules.

Decision making: Making sense of non-sensory neurons.

Decisions can be made internally and implicitly, without being expressed explicitly. A new study reveals how implicit decisions might engage the enigmatic 'non-sensory' neurons in sensory cortex.

Spike-timing-dependent ensemble encoding by non-classically responsive cortical neurons.

Neurons recorded in behaving animals often do not discernibly respond to sensory input and are not overtly task-modulated. These non-classically responsive neurons are difficult to interpret and are typically neglected from analysis, confounding attempts to connect neural activity to perception and behavior. Here, we describe a trial-by-trial, spike-timing-based algorithm to reveal the coding capacities of these neurons in auditory and frontal cortex of behaving rats. Classically responsive and non-classically responsive cells contained significant information about sensory stimuli and behavioral decisions. Stimulus category was more accurately represented in frontal cortex than auditory cortex, via ensembles of non-classically responsive cells coordinating the behavioral meaning of spike timings on correct but not error trials. This unbiased approach allows the contribution of all recorded neurons - particularly those without obvious task-related, trial-averaged firing rate modulation - to be assessed for behavioral relevance on single trials.

More than Just a "Motor": Recent Surprises from the Frontal Cortex.

Motor and premotor cortices are crucial for the control of movements. However, we still know little about how these areas contribute to higher-order motor control, such as deciding which movements to make and when to make them. Here we focus on rodent studies and review recent findings, which suggest that-in addition to motor control-neurons in motor cortices play a role in sensory integration, behavioral strategizing, working memory, and decision-making. We suggest that these seemingly disparate functions may subserve an evolutionarily conserved role in sensorimotor cognition and that further study of rodent motor cortices could make a major contribution to our understanding of the evolution and function of the mammalian frontal cortex.

Long-term recording reliability of liquid crystal polymer µECoG arrays.

OBJECTIVE: The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces. APPROACH: We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (µECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes. In vitro failure modes and predicted lifetimes were determined from accelerated soak testing. Successful designs were implanted epidurally over the rodent auditory cortex. Trends in baseline signal level, evoked responses and decoding performance were reported for over one year of implantation. MAIN RESULTS: Devices fabricated with LCP consistently had longer in vitro lifetimes than PI encapsulation. Our accelerated aging results predicted device integrity beyond 3.4 years. Five implanted arrays showed stable performance over the entire implantation period (247-435 d). Our regression analysis showed that impedance predicted signal quality and information content only in the first 31 d of recordings and had little predictive value in the chronic phase (>31 d). In the chronic phase, site impedances slightly decreased yet decoding performance became statistically uncorrelated with impedance. We also employed an improved statistical model of spatial variation to measure sensitivity to locally varying fields, which is typically concealed in standard signal power calculations. SIGNIFICANCE: These findings show that µECoG arrays can reliably perform in chronic applications in vivo for over one year, which facilitates the development of a high-density, clinically viable interface.

Dynamics of auditory cortical activity during behavioural engagement and auditory perception.

Behavioural engagement can enhance sensory perception. However, the neuronal mechanisms by which behavioural states affect stimulus perception remain poorly understood. Here we record from single units in auditory cortex of rats performing a self-initiated go/no-go auditory task. Self-initiation transforms cortical tuning curves and bidirectionally modulates stimulus-evoked activity patterns and improves auditory detection and recognition. Trial self-initiation decreases the rate of spontaneous activity in the majority of recorded cells. Optogenetic disruption of cortical activity before and during tone presentation shows that these changes in evoked and spontaneous activity are important for sound perception. Thus, behavioural engagement can prepare cortical circuits for sensory processing by dynamically changing sound representation and by controlling the pattern of spontaneous activity.

A low-cost, scalable, current-sensing digital headstage for high channel count µECoG.

OBJECTIVE: High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (µECoG) array. APPROACH: We recorded both acute and chronic µECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. MAIN RESULTS: The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 d. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. SIGNIFICANCE: We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of µECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

A low-cost, multiplexed µECoG system for high-density recordings in freely moving rodents.

OBJECTIVE: Micro-electrocorticography (µECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for µECoG recording in freely moving rats. APPROACH: Multiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections. We have developed a low-cost, multiplexed recording system with 60 contacts at 406 µm spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely moving awake animals. MAIN RESULTS: We recorded µECoG signals over the primary auditory cortex, measuring responses to acoustic stimuli across all channels. Single-trial responses had high signal-to-noise ratios (SNR) (up to 25 dB under anesthesia), and were used to rapidly measure network topography within ∼10 s by constructing all single-channel receptive fields in parallel. We characterized evoked potential amplitudes and spatial correlations across the array in the anesthetized and awake animals. Recording quality in awake animals was stable for at least 30 days. Finally, we used these responses to accurately decode auditory stimuli on single trials. SIGNIFICANCE: This study introduces (1) a µECoG recording system based on practical hardware design and (2) a rigorous analytical method for characterizing the signal characteristics of µECoG electrode arrays. This methodology can be applied to evaluate the fidelity and lifetime of any µECoG electrode array. Our µECoG-based recording system is accessible and will be useful for studies of perception and decision-making in rodents, particularly over the entire time course of behavioral training and learning.

A low-cost, multiplexed electrophysiology system for chronic µECoG recordings in rodents.

Micro-Electrocorticography (µECoG) offers a minimally invasive, high resolution interface with large areas of cortex. However, large arrays of electrodes with many contacts that are individually wired to external recording systems are cumbersome and make chronic recording in freely behaving small animals challenging. Multiplexed headstages overcome this limitation by combining the signals from many electrodes to a smaller number of connections directly on the animal's head. Commercially available multiplexed headstages provide high performance integrated amplification, multiplexing and analog to digital conversion. However, the cost of these systems can be prohibitive for small labs or for experiments that require a large number of animals to be continuously recorded at the same time. Here we have developed a multiplexed 60-channel headstage amplifier optimized to chronically record electrophysiological signals from high-density µECoG electrode arrays. A single, ultraflexible (2 mm thickness) microHDMI cable provided the data interface. Using low cost components, we have reduced the cost of the multiplexed headstage to ~$125. Paired with a custom interface printed circuit board (PCB) and a general purpose data acquisition system (M-series DAQ, National Instruments), an inexpensive and customizable electrophysiology system is assembled. Open source LabVIEW software that we have previously released controlled the system. It can also be used with other open source neural data acquisition packages. Combined, we have presented a scalable, low-cost platform for high-channel count electrophysiology.

Role of hippocampal neurogenesis in mnemonic segregation: implications for human mood disorders.

OBJECTIVES: Although hippocampal neurogenesis has been implicated in mood disorders, the precise role new neurons play in mood regulation is not fully elucidated. Here we examine whether neurogenesis improves mood by facilitating segregation of novel experiences that conflict with older maladaptive memories. METHODS: Study 1: Four groups (N = 9 each) of adult male rats (exposed to stress or control conditions plus antidepressant or placebo) underwent active training on the place-avoidance task (PAT) on week 0; tested on recalling the "Initial PAT" on weeks 4 and 8; learning a subtly "Altered PAT" on week 8; and euthanazed on week 9. Study-2: Two groups (N = 12 each) rats tested either on the Initial-PAT or Altered-PAT 3 days post-training and immediately euthanized. RESULTS: Stressed subjects treated with placebo were slower in learning the week 8 Altered Task and had lower neurogenesis rates than non-stressed animals and Stressed subjects given drug (Study 1). Synaptic activation of mature hippocampal neurons inversely correlated with Altered-PAT performance and with neurogenesis rates (Study 2). CONCLUSIONS: Increasing neurogenesis enhances acquisition of novel experiences possibly by suppressing activation of mature hippocampal neurons that mediate established, conflicting memories. Therefore, antidepressants may improve mood by stimulating new hippocampal neurogenesis that facilitate detection of positive experiences while suppressing interference from recurring depressogenic thought patterns.

Pulsed noise experience disrupts complex sound representations.

Cortical sound representations are adapted to the acoustic environment. Early exposure to exponential frequency-modulated (FM) sweeps results in more neurons selective to the experienced sounds. Here we examined the influence of pulsed noise experience on the development of sound representations in the primary auditory cortex (AI) of the rat. In naïve animals, FM sweep direction selectivity depends on the characteristic frequency (CF) of the neuron--low CF neurons tend to select for upward sweeps and high CF neurons for downward sweeps. Such a CF dependence was not observed in animals that had received weeklong exposure to pulsed noise in periods from postnatal day 8 (P8) to P15 or from P24 to P39. In addition, AI tonotopicity, tuning bandwidth, intensity threshold, tone-responsiveness, and sweep response magnitude were differentially affected by the noise experience depending on the exposure time windows. These results are consistent with previous findings of feature-dependent multiple sensitive periods. The different effects induced here by pulsed noise and previously by FM sweeps further indicate that plasticity in cortical complex sound representations is specific to the sensory input.

Feature-dependent sensitive periods in the development of complex sound representation.

Simple tonal stimuli can shape spectral tuning of cortical neurons during an early epoch of brain development. The effects of complex sound experience on cortical development remain to be determined. We exposed rat pups to a frequency-modulated (FM) sweep in different time windows during early development, and examined the effects of such sensory experience on sound representations in the primary auditory cortex (AI). We found that early exposure to a FM sound resulted in altered characteristic frequency representations and broadened spectral tuning in AI neurons, whereas later exposure to the same sound only led to greater selectivity for the sweep rate and direction of the experienced FM sound. These results indicate that cortical representations of different acoustic features are shaped by complex sounds in a series of distinct sensitive periods.

Early experience impairs perceptual discrimination.

Sensory experience can reorganize cortical sensory representations in an epoch of early development. During this period, cortical sensory neurons may shift their response selectivity and become tuned to more frequently occurring stimuli. Although this enlarged cortical representation is believed to underlie improved sensory processing of the experienced stimuli, its precise perceptual consequences are still unknown. We show that rearing rats in a single-frequency tonal environment results in enlarged cortical representations of the frequencies near that of the experienced tone, but the animals are impaired in perceptual discrimination of the over-represented frequencies. By contrast, discrimination of the neighboring under-represented frequencies is substantially improved. Computational analysis indicated that the altered perceptual ability could be fully accounted for by the sound exposure-induced reorganization of cortical primary auditory representations. These results indicate that early experience shapes sensory perception. The same plasticity processes may be important in optimizing phonemic representations in humans.