Spike sorting with Gaussian mixture models.

The shape of extracellularly recorded action potentials is a product of several variables, such as the biophysical and anatomical properties of the neuron and the relative position of the electrode. This allows isolating spikes of different neurons recorded in the same channel into clusters based on waveform features. However, correctly classifying spike waveforms into their underlying neuronal sources remains a challenge. This process, called spike sorting, typically consists of two steps: (1) extracting relevant waveform features (e.g., height, width), and (2) clustering them into non-overlapping groups believed to correspond to different neurons. In this study, we explored the performance of Gaussian mixture models (GMMs) in these two steps. We extracted relevant features using a combination of common techniques (e.g., principal components, wavelets) and GMM fitting parameters (e.g., Gaussian distances). Then, we developed an approach to perform unsupervised clustering using GMMs, estimating cluster properties in a data-driven way. We found the proposed GMM-based framework outperforms previously established methods in simulated and real extracellular recordings. We also discuss potentially better techniques for feature extraction than the widely used principal components. Finally, we provide a friendly graphical user interface to run our algorithm, which allows manual adjustments.

Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.

Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit.

Receptive field properties of neurons in the electrosensory lateral line lobe of the weakly electric fish, Gnathonemus petersii.

The receptive field of a sensory neuron is known as that region in sensory space where a stimulus will alter the response of the neuron. We determined the spatial dimensions and the shape of receptive fields of electrosensitive neurons in the medial zone of the electrosensory lateral line lobe of the African weakly electric fish, Gnathonemus petersii, by using single cell recordings. The medial zone receives input from sensory cells which encode the stimulus amplitude. We analysed the receptive fields of 71 neurons. The size and shape of the receptive fields were determined as a function of spike rate and first spike latency and showed differences for the two analysis methods used. Spatial diameters ranged from 2 to 36 mm (spike rate) and from 2.45 to 14.12 mm (first spike latency). Some of the receptive fields were simple consisting only of one uniform centre, whereas most receptive fields showed a complex and antagonistic centre-surround organisation. Several units had a very complex structure with multiple centres and surrounding-areas. While receptive field size did not correlate with peripheral receptor location, the complexity of the receptive fields increased from rostral to caudal along the fish's body.

Functional foveae in an electrosensory system.

Several species of Mormyrid weakly electric fish have a mobile chin protuberance that serves as a mobile antenna during prey detection, tracking behaviors, and foraging for food. It has been proposed that it constitutes a fovea of the electrosensory system. The distribution of the three types of receptor organs involved in active imaging of the local surroundings, prey detection, and passive electroreception, and their central projection to the electrosensory lobe (ELL), have been studied in Gnathonemus petersii. Density distributions were compared for different body regions. Primary afferent projections were labeled with biocytin or biotinylated dextrans. This showed that there is considerable central "over-representation" of the mandibular and nasal regions of the sensory surface involved in electrolocation, at the expense of the other body regions investigated. This over-representation is not a mere effect of the very high density of receptor organs in these areas, but is found to be due to central magnification. This magnification differs between the subclasses of electroreceptors, suggesting a functional segregation in the brain. We conclude that the chin protuberance and the nasal region are the regions of greatest sensitivity for the resistive, capacitive, and low-frequency characteristics of the environment, and are probably most important in prey detection, whereas other regions of the skin with a lesser resolution and sensitivity to phase distortion of the EOD, in particular the trunk, are probably designed for imaging larger, inanimate features of the environment. Our data support the hypothesis that the chin appendage and nasal region are functionally distinct electrosensory foveae.

Electric imaging through active electrolocation: implication for the analysis of complex scenes.

The electric sense of mormyrids is often regarded as an adaptation to conditions unfavourable for vision and in these fish it has become the dominant sense for active orientation and communication tasks. With this sense, fish can detect and distinguish the electrical properties of the close environment, measure distance, perceive the 3-D shape of objects and discriminate objects according to distance or size and shape, irrespective of conductivity, thus showing a degree of abstraction regarding the interpretation of sensory stimuli. The physical properties of images projected on the sensory surface by the fish's own discharge reveal a "Mexican hat" opposing centre-surround profile. It is likely that computation of the image amplitude to slope ratio is used to measure distance, while peak width and slope give measures of shape and contrast. Modelling has been used to explore how the images of multiple objects superimpose in a complex manner. While electric images are by nature distributed, or 'blurred', behavioural strategies orienting sensory surfaces and the neural architecture of sensory processing networks both contribute to resolving potential ambiguities. Rostral amplification is produced by current funnelling in the head and chin appendage regions, where high density electroreceptor distributions constitute foveal regions. Central magnification of electroreceptive pathways from these regions particularly favours the detection of capacitive properties intrinsic to potential living prey. Swimming movements alter the amplitude and contrast of pre-receptor object-images but image modulation is normalised by central gain-control mechanisms that maintain excitatory and inhibitory balance, removing the contrast-ambiguity introduced by self-motion in much the same way that contrast gain-control is achieved in vision.

Active sensing in a mormyrid fish: electric images and peripheral modifications of the signal carrier give evidence of dual foveation.

Weakly electric fish generate electric fields with an electric organ and perceive them with cutaneous electroreceptors. During active electrolocation, nearby objects are detected by the distortions they cause in the electric field. The electrical properties of objects, their form and their distance, can be analysed and distinguished. Here we focus on Gnathonemus petersii (Günther 1862), an African fish of the family Mormyridae with a characteristic chin appendix, the Schnauzenorgan. Behavioural and anatomical results suggest that the mobile Schnauzenorgan and the nasal region serve special functions in electroreception, and can therefore be considered as electric foveae. We investigated passive pre-receptor mechanisms that shape and enhance the signal carrier. These mechanisms allow the fish to focus the electric field at the tip of its Schnauzenorgan where the density of electroreceptors is highest (tip-effect). Currents are funnelled by the open mouth (funnelling-effect), which leads to a homogenous voltage distribution in the nasal region. Field vectors at the trunk, the nasal region and the Schnauzenorgan are collimated but differ in the angle at which they are directed onto the sensory surface. To investigate the role of those pre-receptor effects on electrolocation, we recorded electric images of objects at the foveal regions. Furthermore, we used a behavioural response (novelty response) to assess the sensitivity of different skin areas to electrolocation stimuli and determined the receptor densities of these regions. Our results imply that both regions - the Schnauzenorgan and the nasal region - can be termed electric fovea but they serve separate functions during active electrolocation.

Etomidate reduces initiation of backpropagating dendritic action potentials: implications for sensory processing and synaptic plasticity during anesthesia.

Anesthetics may induce specific changes that alter the balance of activity within neural networks. Here we describe the effects of the GABA(A) receptor potentiating anesthetic etomidate on sensory processing, studied in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in vitro. Previous studies have shown that the ELL integrates sensory input and removes predictable features by comparing reafferent sensory signals with a descending electromotor command-driven corollary signal that arrives in part through parallel fiber synapses with the apical dendrites of GABAergic interneurons. These synapses show spike timing-dependent depression when presynaptic activation is associated with postsynaptic backpropagating dendritic action potentials. Under etomidate, almost all neurons become tonically hyperpolarized. The threshold for action potential initiation increased for both synaptic activation and direct intracellular depolarization. Synaptically evoked inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and prolonged. Current source density analysis showed that backpropagation of action potentials through the apical dendritic arborization in the molecular layer was reduced but could be restored by increasing stimulus strength. These effects of etomidate were blocked by bicuculline or picrotoxin. It is concluded that etomidate affects both tonic and phasic inhibitory conductances at GABA(A) receptors and that increased shunting inhibition at the level of the proximal dendrites also contributes to increasing the threshold for action potential backpropagation. When stimulus strength is sufficient to evoke backpropagation, repetitive association of synaptic excitation with postsynaptic action potential initiation still results in synaptic depression, showing that etomidate does not interfere with the molecular mechanism underlying plastic modulation.

Sensory and motor effects of etomidate anesthesia.

The effects of anesthesia with etomidate on the cellular mechanisms of sensory processing and sensorimotor coordination have been studied in the active electric sense of the mormyrid fish Gnathonemus petersii. Like many anesthetics, etomidate is known to potentiate GABA(A) receptors, but little is known about the effects on sensory processing at the systems level. A better understanding is necessary for experimental studies of sensory processing, in particular regarding possible effects on the dynamic structure of excitatory and inhibitory receptive fields and to improve the knowledge of the mechanisms of anesthesia in general. Etomidate slowed the electromotor discharge rhythm, probably because of feedback inhibition at the premotor level, but did not alter the structure of the electromotor command. Sensory translation through primary afferents projecting to the cerebellum-like electrosensory lobe (ELL) was not changed. However, central interneurons and projection neurons were hyperpolarized under etomidate, and their spiking activity was reduced. Although the spatial extent and the center/surround organization of sensory receptive fields were not changed, initial excitatory responses were followed by prolonged inhibition. Corollary discharge input to ELL was maintained, and the temporal sequence of excitatory and inhibitory components of this descending signal remained intact. Later inhibitory corollary discharge responses were prolonged by several hundred milliseconds. The result was that excitatory reafferent sensory input was conserved with enhanced precision of timing, whereas background activity was greatly reduced. Anti-Hebbian synaptic plasticity evoked by association of sensory and corollary discharge input was still present under anesthesia, and differences compared with the nonanesthetized condition are discussed.