Modulation of auditory responses by modality-specific attention in rat primary auditory cortex

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Here we describe results of experiments in freely moving rats in which we have used tetrodes to record neural responses in primary auditory cortex (area A1) while subjects performed this behavior.

Subjects were first trained to perform distinct auditory and olfactory two alternative forced-choice (2AFC) tasks. Training and testing were conducted in a custom three-poke computer-controlled behavioral apparatus. Subjects initiated trials with a center-poke, which triggered presentation of a tone (either 5 or 15 Hz), an odor (either R(-)-2-Octanol or S(+)-2-Octanol), or both. Subjects responded moving to the left or right poke. Correct responses were rewarded with water. Auditory and olfactory blocks (of 50 trials each) were interleaved in a single session. In auditory blocks, pure tones were either presented with or without a null odor (caproic acid, n=2 and 3 respectively), and subjects were cued to perform the task based on auditory stimuli. In olfactory blocks, both odors and pure tones were presented simultaneously, and subjects were cued to perform the task based on olfactory stimuli.

After subjects reached consistent performance on the interleaved blocks, tetrode drives were implanted in primary auditory cortex of the left hemisphere. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. Among 304 responsive units recorded, 19% (58 units) showed modality-specific attentional modulation of at least one of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). In addition, we also observed modality-specific attentional modulation of the spontaneous activity in similar proportion of units (61 units). 

Our results suggest that shifting attention from audition to olfaction and back can modulate the activity of single neurons in primary auditory cortex

Neural Mechanisms of Selective Auditory Attention in Rats (Dissertation)

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Rats were trained to perform distinct auditory two-tone discrimination and olfactory odor discrimination in a two alternative choice (2AC) paradigm. 
To determine auditory cortex’s role in this frequency discrimination task, we used GABA-A receptor agonist muscimol to transiently and reversibly inactivate auditory cortexes bilaterally in rats performing simple interleaved auditory and olfactory discrimination. With olfactory discrimination performance serving as internal control for motivation and decision making capability, we found only auditory two-tone discrimination was selectively impaired in these rats. This shows the auditory cortex is involved in this two-tone discrimination task.
To investigate the neural correlate of modality-specific attention in the auditory cortex, we trained rats to perform interleaved auditory and olfactory blocks (of 50~70 trials each) in a single session. In auditory blocks, pure tones were either presented with or without a neutral odor (caproic acid, n=2 and 3 respectively), and subjects were rewarded for discriminating auditory stimuli. In olfactory blocks, both task odors and pure tones were presented simultaneously, and subjects were rewarded for discriminating olfactory stimuli. We recorded neural responses in primary auditory cortex (area A1) in freely moving rats while subjects performed this behavior. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. We found 205 of 802 units recorded responsive to the stimuli we used. Of these 205 units, 18.5% showed modality-specific attentional modulation of the anticipatory activity before tone onset. In addition, we also observed in smaller proportion of units (11.2%) modality-specific attentional modulation of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). Attention increased choice probability of the population in the auditory block. We have also observed significant behavior choice probability in small proportions of units. 
Our results suggest that shifting attention between audition to olfaction tasks can modulate the activity of single neurons in primary auditory cortex

Correlated connectivity and the distribution of firing rates in the neocortex

Two recent experimental observations pose a challenge to many cortical models. First, the activity in the auditory cortex is sparse, and firing rates can be described by a lognormal distribution. Second, the distribution of non-zero synaptic strengths between nearby cortical neurons can also be described by a lognormal distribution. Here we use a simple model of cortical activity to reconcile these observations. The model makes the experimentally testable prediction that synaptic efficacies onto a given cortical neuron are statistically correlated, i.e. it predicts that some neurons receive many more strong connections than other neurons. We propose a simple Hebb-like learning rule which gives rise to both lognormal firing rates and synaptic efficacies. Our results represent a first step toward reconciling sparse activity and sparse connectivity in cortical networks

Non-Gaussian membrane potential dynamics imply sparse, synchronous activity in auditory cortex

Many models of cortical dynamics have focused on the high-firing regime, in which neurons are driven near their maximal rate. Here we consider the responses of neurons in auditory cortex under typical low-firing rate conditions, when stimuli have not been optimized to drive neurons maximally. We used whole-cell patch-clamp recording in vivo to measure subthreshold membrane potential fluctuations in rat primary auditory cortex in both the anesthetized and awake preparations. By analyzing the subthreshold membrane potential dynamics on single trials, we made inferences about the underlying population activity. We found that, during both spontaneous and evoked responses, membrane potential was highly non-Gaussian, with dynamics consisting of occasional large excursions (sometimes tens of millivolts), much larger than the small fluctuations predicted by most random walk models that predict a Gaussian distribution of membrane potential. Thus, presynaptic inputs under these conditions are organized into quiescent periods punctuated by brief highly synchronous volleys, or "bumps." These bumps were typically so brief that they could not be well characterized as "up states" or "down states." We estimate that hundreds, perhaps thousands, of presynaptic neurons participate in the largest volleys. These dynamics suggest a computational scheme in which spike timing is controlled by concerted firing among input neurons rather than by small fluctuations in a sea of background activity

Sources of PCR-induced distortions in high-throughput sequencing data sets

PCR permits the exponential and sequence-specific amplification of DNA, even from minute starting quantities. PCR is a fundamental step in preparing DNA samples for high-throughput sequencing. However, there are errors associated with PCR-mediated amplification. Here we examine the effects of four important sources of error-bias, stochasticity, template switches and polymerase errors-on sequence representation in low-input next-generation sequencing libraries. We designed a pool of diverse PCR amplicons with a defined structure, and then used Illumina sequencing to search for signatures of each process. We further developed quantitative models for each process, and compared predictions of these models to our experimental data. We find that PCR stochasticity is the major force skewing sequence representation after amplification of a pool of unique DNA amplicons. Polymerase errors become very common in later cycles of PCR but have little impact on the overall sequence distribution as they are confined to small copy numbers. PCR template switches are rare and confined to low copy numbers. Our results provide a theoretical basis for removing distortions from high-throughput sequencing data. In addition, our findings on PCR stochasticity will have particular relevance to quantification of results from single cell sequencing, in which sequences are represented by only one or a few molecules

Mice and rats achieve similar levels of performance in an adaptive decision-making task

Two opposing constraints exist when choosing a model organism for studying the neural basis of adaptive decision-making: (1) experimental access and (2) behavioral complexity. Available molecular and genetic approaches for studying neural circuits in the mouse fulfill the first requirement. In contrast, it is still under debate if mice can perform cognitive tasks of sufficient complexity. Here we compare learning and performance of mice and rats, the preferred behavioral rodent model, during an acoustic flexible categorization two-alternative choice task. The task required animals to switch between two categorization definitions several times within a behavioral session. We found that both species achieved similarly high performance levels. On average, rats learned the task faster than mice, although some mice were as fast as the average rat. No major differences in subjective categorization boundaries or the speed of adaptation between the two species were found. Our results demonstrate that mice are an appropriate model for the study of the neural mechanisms underlying adaptive decision-making, and suggest they might be suitable for other cognitive tasks as well

VC Dimension of an Integrate-and-Fire Neuron Model

We find the VC dimension of a leaky integrate-and-fire neuron model. The VC dimension quantifies the ability of a function class to partition an input pattern space, and can be considered a measure of computational capacity. In this case, the function class is the class of integrate-and-fire models generated by varying the integration time constant τ and the threshold ϴ, the input space they partition is the space of continuous-time signals, and the binary partition is specified by whether or not the model reaches threshold and spikes at some specified time. We show that the VC dimension diverges only logarithmically with the input signal bandwidth N , where the signal bandwidth is determined by the noise inherent in the process of spike generation. For reasonable estimates of the signal bandwidth, the VC dimension turns out to be quite small (¡10). We also extend this approach to ar- bitrary passive dendritic trees. The main contributions of this work are (1) it offers a novel treatment of the computational capacity of this class of dynamic system; and (2) it provides a framework for analyzing the computational capabilities of the dynamical systems defined by networks of spiking neurons

Sparse representation of sounds in the unanesthetized auditory cortex

How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli) in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second) in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second). At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons

Auditory Thalamus and Auditory Cortex Are Equally Modulated by Context during Flexible Categorization of Sounds

In a dynamic world, animals must adapt rapidly to changes in the meaning of environmental cues. Such changes can influence the neural representation of sensory stimuli. Previous studies have shown that associating a stimulus with a reward or punishment can modulate neural activity in the auditory cortex (AC) and its thalamic input, the medial geniculate body (MGB). However, it is not known whether changes in stimulus-action associations alone can also modulate neural responses in these areas. We designed a categorization task for rats in which the boundary that separated low- from high-frequency sounds varied several times within a behavioral session, thus allowing us to manipulate the action associated with some sounds without changing the associated reward. We developed a computational model that accounted for the rats' performance and compared predictions from this model with sound-evoked responses from single neurons in AC and MGB in animals performing this task. We found that the responses of 15% of AC neurons and 16% of MGB neurons were modulated by changes in stimulus-action association and that the magnitude of the modulation was comparable between the two brain areas. Our results suggest that the AC and thalamus play only a limited role in mediating changes in associations between acoustic stimuli and behavioral responses