Michael R. Bale

Diverse and Temporally Precise Kinetic Feature Selectivity in the VPm Thalamic Nucleus

The thalamo-cortical pathway is the crucial sensory gateway into the cerebral cortex. We aimed to determine the nature of the tactile information encoded by neurons in the whisker somatosensory relay nucleus (VPm). We wanted to distinguish whether VPm neurons encode similar stimulus features, acting as a single information channel, or encode diverse features. We recorded responses to whisker deflections that thoroughly explored the space of temporal stimulus variables and identified features to which neurons were selective by reverse correlation. The timescale of the features was typically 1-2 ms, at the limit imposed by our experimental conditions, indicating highly acute feature selectivity. Sensitivity to stimulus kinetics was strikingly diverse. Some neurons (25%) only encoded velocity; others were sensitive to position, acceleration, or more complex features. A minority (19%) encoded two or more features. These results indicate that VPm contains a distributed representation of whisker motion, based on high-resolution kinetic features.

Transformation in the neural code for whisker deflection direction along the lemniscal pathway.

A prominent characteristic of neurons in the whisker system is their selectivity to the direction in which a whisker is deflected. The aim of this study was to determine how information about whisker direction is encoded at successive levels of the lemniscal pathway. We made extracellular recordings under identical conditions from the trigeminal ganglion, ventro-posterior medial thalamus (VPM), and barrel cortex while varying the direction of whisker deflection. We found a marked increase in the variability of single unit responses along the pathway. To study the consequences of this for information processing, we quantified the responses using mutual information. VPM units conveyed 48% of the mutual information conveyed by ganglion units, and cortical units conveyed 12%. The fraction of neuronal bandwidth used for transmitting direction information decreased from 40% in the ganglion to 24% in VPM and 5% in barrel cortex. To test whether, in cortex, population coding might compensate for this information loss, we made simultaneous recordings. We found that cortical neuron pairs conveyed 2.1 times the mutual information conveyed by single neurons. Overall, these findings indicate a marked transformation from a subcortical neural code based on small numbers of reliable neurons to a cortical code based on populations of unreliable neurons. However, the basic form of the neural code in ganglion, thalamus, and cortex was similar-at each stage, the first poststimulus spike carried the majority of the information.

Prediction of primary somatosensory neuron activity during active tactile exploration

Primary sensory neurons form the interface between world and brain. Their function is well-understood during passive stimulation but, under natural behaving conditions, sense organs are under active, motor control. In an attempt to predict primary neuron firing under natural conditions of sensorimotor integration, we recorded from primary mechanosensory neurons of awake, head-fixed mice as they explored a pole with their whiskers, and simultaneously measured both whisker motion and forces with high-speed videography. Using Generalised Linear Models, we found that primary neuron responses were poorly predicted by whisker angle, but well-predicted by rotational forces acting on the whisker: both during touch and free-air whisker motion. These results are in apparent contrast to previous studies of passive stimulation, but could be reconciled by differences in the kinematics-force relationship between active and passive conditions. Thus, simple statistical models can predict rich neural activity elicited by natural, exploratory behaviour involving active movement of sense organs. DOI: http://dx.doi.org/10.7554/eLife.10696.001

Low-Dimensional Sensory Feature Representation by Trigeminal Primary Afferents

In any sensory system, the primary afferents constitute the first level of sensory representation and fundamentally constrain all subsequent information processing. Here, we show that the spike timing, reliability, and stimulus selectivity of primary afferents in the whisker system can be accurately described by a simple model consisting of linear stimulus filtering combined with spike feedback. We fitted the parameters of the model by recording the responses of primary afferents to filtered, white noise whisker motion in anesthetized rats. The model accurately predicted not only the response of primary afferents to white noise whisker motion (median correlation coefficient 0.92) but also to naturalistic, texture-induced whisker motion. The model accounted both for submillisecond spike-timing precision and for non-Poisson spike train structure. We found substantial diversity in the responses of the afferent population, but this diversity was accurately captured by the model: a 2D filter subspace, corresponding to different mixtures of position and velocity sensitivity, captured 94% of the variance in the stimulus selectivity. Our results suggest that the first stage of the whisker system can be well approximated as a bank of linear filters, forming an overcomplete representation of a low-dimensional feature space.

Comparison of latency and rate coding for the direction of whisker deflection in the subcortical somatosensory pathway

The response of many neurons in the whisker somatosensory system depends on the direction in which a whisker is deflected. Although it is known that the spike count conveys information about this parameter, it is not known how important spike timing might be. The aim of this study was to compare neural codes based on spike count and first-spike latency, respectively. We extracellularly recorded single units from either the rat trigeminal ganglion (primary sensory afferents) or ventroposteromedial (VPM) thalamic nucleus in response to deflection in different directions and quantified alternative neural codes using mutual information. We found that neurons were diverse: some (58% in ganglion, 32% in VPM) conveyed information only by spike count; others conveyed additional information by latency. An issue with latency coding is that latency is measured with respect to the time of stimulus onset, a quantity known to the experimenter but not directly to the subjects brain. We found a potential solution using the integrated population activity as an internal timing signal: in this way, 91% of the first-spike latency information could be recovered. Finally, we asked how well direction could be decoded. For large populations, spike count and latency codes performed similarly; for small ones, decoding was more accurate using the latency code. Our findings indicate that whisker deflection direction is more efficiently encoded by spike timing than by spike count. Spike timing decreases the population size necessary for reliable information transmission and may thereby bring significant advantages in both wiring and metabolic efficiency.

Transformation of adaptation and gain rescaling along the whisker sensory pathway.

Neurons in all sensory systems have a remarkable ability to adapt their sensitivity to the statistical structure of the sensory signals to which they are tuned. In the barrel cortex, firing rate adapts to the variance of a whisker stimulus and neuronal sensitivity (gain) adjusts in inverse proportion to the stimulus standard deviation. To determine how adaptation might be transformed across the ascending lemniscal pathway, we measured the responses of single units in the first and last subcortical stages, the trigeminal ganglion (TRG) and ventral posterior medial thalamic nucleus (VPM), to controlled whisker stimulation in urethane-anesthetized rats. We probed adaptation using a filtered white noise stimulus that switched between low- and high-variance epochs. We found that the firing rate of both TRG and VPM neurons adapted to stimulus variance. By fitting the responses of each unit to a Linear-Nonlinear-Poisson model, we tested whether adaptation changed feature selectivity and/or sensitivity. We found that, whereas feature selectivity was unaffected by stimulus variance, units often exhibited a marked change in sensitivity. The extent of these sensitivity changes increased systematically along the pathway from TRG to barrel cortex. However, there was marked variability across units, especially in VPM. In sum, in the whisker system, the adaptation properties of subcortical neurons are surprisingly diverse. The significance of this diversity may be that it contributes to a rich population representation of whisker dynamics.

Efficient population coding of naturalistic whisker motion in the ventro-posterior medial thalamus based on precise spike timing

The rodent whisker-associated thalamic nucleus (VPM) contains a somatotopic map where whisker representation is divided into distinct neuronal sub-populations, called “barreloids”. Each barreloid projects to its associated cortical barrel column and so forms a gateway for incoming sensory stimuli to the barrel cortex. We aimed to determine how the population of neurons within one barreloid encodes naturalistic whisker motion. In rats, we recorded the extracellular activity of up to nine single neurons within a single barreloid, by implanting silicon probes parallel to the longitudinal axis of the barreloids. We found that play-back of texture-induced whisker motion evoked sparse responses, timed with millisecond precision. At the population level, there was synchronous activity: however, different subsets of neurons were synchronously active at different times. Mutual information between population responses and whisker motion increased near linearly with population size. When normalized to factor out firing rate differences, we found that texture was encoded with greater informational-efficiency than white noise. These results indicate that, within each VPM barreloid, there is a rich and efficient population code for naturalistic whisker motion based on precisely timed, population spike patterns.

Organization of sensory feature selectivity in the whisker system

Highlights • Neurons in the whisker system are selective to spatial and dynamical properties – features – of sensory stimuli.• At each stage of the pathway, different neurons encode distinct features, generating a rich population representation.• Whisker touch is robustly represented; neurons respond to touch-driven fast fluctuations in forces at the whisker base.• Cortical neurons have more complex and context-dependent selectivity than subcortical, e.g., to collective whisker motion.• Understanding how these signals are integrated to construct whisker-mediated percepts requires further research.

Learning and recognition of tactile temporal sequences by mice and humans

The world around us is replete with stimuli that unfold over time. When we hear an auditory stream like music or speech or scan a texture with our fingertip, physical features in the stimulus are concatenated in a particular order. This temporal patterning is critical to interpreting the stimulus. To explore the capacity of mice and humans to learn tactile sequences, we developed a task in which subjects had to recognise a continuous modulated noise sequence delivered to whiskers or fingertips, defined by its temporal patterning over hundreds of milliseconds. GO and NO-GO sequences differed only in that the order of their constituent noise modulation segments was temporally scrambled. Both mice and humans efficiently learned tactile sequences. Mouse sequence recognition depended on detecting transitions in noise amplitude; animals could base their decision on the earliest information available. Humans appeared to use additional cues, including the duration of noise modulation segments. DOI: http://dx.doi.org/10.7554/eLife.27333.001

Phase-of-firing coding of dynamical whisker stimuli and the thalamocortical code in barrel cortex

In the phase-of-firing (PoF) code the information carried by spikes is boosted when their firing is measured against the angular phase of the local extracellular signal. This coding strategy has been verified so far in visual and auditory cortices of monkeys at low frequencies [1,2]. Here we present the first evidence of this code in whisker modality. In particular, we characterise the PoF encoding of the white-noise whisker deflections in the barrel cortex responses of urethane anaesthetized rats. A novel aspect of our results is identifying the high frequency components of the PoF responses at certain cortical layers, with implications regarding the thalamo-cortical code and cortical information processing. The results indicate that the amount of information encoded using a PoF code was on average 100% greater than a spike rate code using MUA (Figure ​(Figure1A),1A), and this was up to 250% in deeper channels of the cortical columns. Contrary to the previous findings [1,2], the extra information in PoF using LFP was peaked at very high frequencies (100 Hz). The effect extended to >200 Hz bands of LFP. When CSD was used for labelling spikes, the effect was more localized with respect to depth, and was peaked at different frequencies at different cortical layers (Figure ​(Figure1C).1C). The depth-frequency profile was consistent across the multi-channel electrode penetrations. Why the PoF information was maximal at such high-frequency bands? ( >100 Hz) We hypothesised that the high-frequency PoF components originated from the high-frequency components in the white-noise stimuli. The depth-frequency profile and CSD analysis of layers showed association of the high-frequency components of PoF with the cortical layers that are known to receive direct thalamo-cortical input from VPM. A similar pattern was previously suggested in [5]. The high-frequency components of CSD phase responses were weak or absent in layers that are not associated with such projections (Figure ​(Figure1C1C). Figure 1 A. Phase-of-firing information and and spike rate information averaged across channels. B. Depth-frequency profile of the CSD phase information across the cortical layers (for two electrodes in two animals). C. same as B, but normalised to reveal the ... We then examined whether the pure spiking activity contributes in the information manifested in the high frequency PoF components. The temporal precision of spikes was quantified using a novel measure, information in the phase of the band-bass filtered spike trains. In all depths, the spikes lacked any temporal-resolution larger than 30 Hz (Figure ​(Figure1D).1D). We conclude that the output of the local computational processes in a cortical column lacked the temporal precision that they received in input (i.e., which was represented by CSD). This suggests a transformation of the information encoding from a high-precision input code relayed from thalamus, with fast and temporally precise dynamics (see [4]), into an output spiking code with a lower temporal resolution. Nevertheless, information about the high-frequency and fast varying components of the stimulus may still be encoded within the low resolution and irregular cortical spikes. In fact previous studies have shown that a spike-count code in the cortex can encode such stimulus features [3]. The computational demands of the whisker system (such as fine texture discrimination, and perception of subtle vibrations in the air) require that the thalamus relays the high-frequency components of the whisker deflections into the cortical barrels, which are capable of performing more complex neural computation.