Octopus Cells Research Articles

A computational model of auditory chirp-velocity sensitivity and amplitude-modulation tuning in inferior colliculus neurons.

We demonstrate a model of chirp-velocity sensitivity in the inferior colliculus (IC) that retains the tuning to amplitude modulation (AM) that was established in earlier models. The mechanism of velocity sensitivity is sequence detection by octopus cells of the posteroventral cochlear nucleus, which have been proposed in physiological studies to respond preferentially to the order of arrival of cross-frequency inputs of different amplitudes. Model architecture is based on coincidence detection of a combination of excitatory and inhibitory inputs. Chirp-sensitivity of the IC output is largely controlled by the strength and timing of the chirp-sensitive octopus-cell inhibitory input. AM tuning is controlled by inhibition and excitation that are tuned to the same frequency. We present several example neurons that demonstrate the feasibility of the model in simulating realistic chirp-sensitivity and AM tuning for a wide range of characteristic frequencies. Additionally, we explore the systematic impact of varying parameters on model responses. The proposed model can be used to assess the contribution of IC chirp-velocity sensitivity to responses to complex sounds, such as speech.

An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System.

Animals navigate the auditory world by recognizing complex sounds, from the rustle of a predator to the call of a potential mate. This ability depends in part on the octopus cells of the auditory brainstem, which respond to multiple frequencies that change over time, as occurs in natural stimuli. Unlike the average neuron, which integrates inputs over time on the order of tens of milliseconds, octopus cells must detect momentary coincidence of excitatory inputs from the cochlea during an ongoing sound on both the millisecond and submillisecond time scale. Here, we show that octopus cells receive inhibitory inputs on their dendrites that enhance opportunities for coincidence detection in the cell body, thereby allowing for responses both to rapid onsets at the beginning of a sound and to frequency modulations during the sound. This mechanism is crucial for the fundamental process of integrating the synchronized frequencies of natural auditory signals over time.

A Computational Model of Auditory Chirp-Velocity Sensitivity and Amplitude-Modulation Tuning in Inferior Colliculus Neurons.

We demonstrate a model of chirp-velocity sensitivity in the inferior colliculus (IC) that retains the tuning to amplitude modulation (AM) that was established in earlier models. The mechanism of velocity sensitivity is sequence detection by octopus cells of the posteroventral cochlear nucleus, which have been proposed in physiological studies to respond preferentially to the order of arrival of cross-frequency inputs of different amplitudes. Model architecture is based on coincidence detection of a combination of excitatory and inhibitory inputs. Chirp-sensitivity of the IC output is largely controlled by the strength and timing of the chirp-sensitive octopus-cell inhibitory input. AM tuning is controlled by inhibition and excitation that are tuned to the same frequency. We present several example neurons that demonstrate the feasibility of the model in simulating realistic chirp-sensitivity and AM tuning for a wide range of characteristic frequencies. Additionally, we explore the systematic impact of varying parameters on model responses. The proposed model can be used to assess the contribution of IC chirp-velocity sensitivity to responses to complex sounds, such as speech.

Glycine is a transmitter in the human and chimpanzee cochlear nuclei.

Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and circuitry of the cochlear nuclei (CN) have been studied in many species. It is well-established that glycine is an inhibitory transmitter in the CN of rodents and cats, with glycinergic cells in the DCN and VCN. There are, however, major differences in the laminar and cellular organization of the DCN between humans (and other primates) and rodents and cats. We therefore asked whether there might also be differences in glycinergic neurotransmission in the CN. We studied brainstem sections from humans, chimpanzees, and cats. We used antibodies to glycine receptors (GLYR) to identify neurons receiving glycinergic input, and antibodies to the neuronal glycine transporter (GLYT2) to immunolabel glycinergic axons and terminals. We also examined archival sections immunostained for calretinin (CR) and nonphosphorylated neurofilament protein (NPNFP) to try to locate the octopus cell area (OCA), a region in the VCN that rodents has minimal glycinergic input. In humans and chimpanzees we found widespread immunolabel for glycine receptors in DCN and in the posterior (PVCN) and anterior (AVCN) divisions of the VCN. We found a parallel distribution of GLYT2-immunolabeled fibers and puncta. The data also suggest that, as in rodents, a region containing octopus cells in cats, humans and chimpanzees has little glycinergic input. Our results show that glycine is a major transmitter in the human and chimpanzee CN, despite the species differences in DCN organization. The sources of the glycinergic input to the CN in humans and chimpanzees are not known.

The switching and learning behavior of an octopus cell implemented on FPGA.

A dendrocentric backpropagation spike timing-dependent plasticity learning rule has been derived based on temporal logic for a single octopus neuron. It receives parallel spike trains and collectively adjusts its synaptic weights in the range [0, 1] during training. After the training phase, it spikes in reaction to event signaling input patterns in sensory streams. The learning and switching behavior of the octopus cell has been implemented in field-programmable gate array (FPGA) hardware. The application in an FPGA is described and the proof of concept for its application in hardware that was obtained by feeding it with spike cochleagrams is given; also, it is verified by performing a comparison with the pre-computed standard software simulation results.

What, if anything, is coincidence detection?

Neural delays and coincidence detection are neural operations posited as key elements in temporal processing, in the auditory system and beyond. Although longstanding physiological evidence for coincidence detectors exists at a phenomenological level, mechanistic examinations have only recently been performed. We review intracellular recordings from two cell types which are traditionally regarded as prototypes of coincidence detectors. Neurons in the medial superior olive (MSO) are sensitive to “coincidences” in action potentials from the ipsi- and contralateral ear, making the neurons sensitive to interaural temporal differences. Octopus cells in the cochlear nucleus are sensitive to “coincidences” of action potentials across inputs tuned to a wide range of frequencies. We found that in both cases, the spike output of neurons does not simply reflect coincidences of input spikes. When inputs vary in strength, their sequence of activation is an important determinant of response strength. Maximal output is not just determined by the maximal number of coincidences, but reflects temporal input structure in interaction with intrinsic (membrane) properties. These observations suggest a simpler mechanism of temporal sensitivity than traditional lag and coincidence proposals.

Mammalian octopus cells are direction selective to frequency sweeps by excitatory synaptic sequence detection

Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide-frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized invivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from across-frequency coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of hot spot frequencies. A simple biophysical octopus cell model excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with the activation sequence of clustered excitatory inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.

Physiological sensitivity to across-channel temporal patterns in response to Schroeder harmonic complexes, based on sequence rather than coincidence detection

The flat-envelope harmonic complexes devised by Schroeder (1970) contain a linear frequency sweep whose direction and speed depend on phase curvature C. Physiological studies have focused on responses at a given characteristic frequency (CF), which show only a subtle dependence on the sign and magnitude of C. The question arises whether CNS neurons are sensitive to the temporal pattern across nerve fibers differing in CF. Octopus cells in the cochlear nucleus receive convergent excitatory input from nerve fibers spanning a wide range of CFs and are thought to be monaural coincidence detectors. We studied their spike output and membrane responses to Schroeder complexes in anesthetized gerbils. Octopus cells were indeed tuned to a wide frequency range but showed discrete frequency “hotspots” of differing strength. Most cells showed marked sensitivity to C, with some neurons preferring upward and others downward frequency sweeps, which was broadly stable across SPL and fundamental frequency. The sensitivity to C arises not from coincidence detection, but from a sensitivity to the temporal sequence of activation of inputs tuned to different frequencies. We conclude that marked sensitivity to Schroeder phase exists at the first CNS processing stage and is based on temporal sequence detection across frequency channels.

Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility.

Neuromorphic computer models are used to explain sensory perceptions. Auditory models generate cochleagrams, which resemble the spike distributions in the auditory nerve. Neuron ensembles along the auditory pathway transform sensory inputs step by step and at the end pitch is represented in auditory categorical spaces. In two previous articles in the series on periodicity pitch perception an extended auditory model had been successfully used for explaining periodicity pitch proved for various musical instrument generated tones and sung vowels. In this third part in the series the focus is on octopus cells as they are central sensitivity elements in auditory cognition processes. A powerful numerical model had been devised, in which auditory nerve fibers (ANFs) spike events are the inputs, triggering the impulse responses of the octopus cells. Efficient algorithms are developed and demonstrated to explain the behavior of octopus cells with a focus on a simple event-based hardware implementation of a layer of octopus neurons. The main finding is, that an octopus' cell model in a local receptive field fine-tunes to a specific trajectory by a spike-timing-dependent plasticity (STDP) learning rule with synaptic pre-activation and the dendritic back-propagating signal as post condition. Successful learning explains away the teacher and there is thus no need for a temporally precise control of plasticity that distinguishes between learning and retrieval phases. Pitch learning is cascaded: At first octopus cells respond individually by self-adjustment to specific trajectories in their local receptive fields, then unions of octopus cells are collectively learned for pitch discrimination. Pitch estimation by inter-spike intervals is shown exemplary using two input scenarios: a simple sinus tone and a sung vowel. The model evaluation indicates an improvement in pitch estimation on a fixed time-scale.

Sensitivity to Schroeder phase arising from sensitivity to temporal patterns across nerve fibers

The flat-envelope harmonic complexes devised by Schroeder (1970) have been extensively used in psychophysical studies. The stimuli contain a linear frequency sweep, whose direction and speed depend on phase curvature C. For a given characteristic frequency, basilar membrane and nerve responses show only a subtle dependence on the sign and magnitude of C. The question arises whether CNS neurons are sensitive to the temporal pattern across nerve fibers. We studied octopus cells in the cochlear nucleus, which receive a convergent excitatory input from nerve fibers and have been hypothesized to be monaural coincidence detectors. We studied both their spike output and nerve input using multiple recording techniques in anesthetized chinchillas. Octopus cells showed marked sensitivity to C, which was broadly stable across SPL and fundamental frequency. They were tuned to a wide frequency range, but with discrete frequency “hotspots” that generate major and minor inputs. The sensitivity to C arises not from coincidence detection, but from a sensitivity to the temporal sequence of activation of inputs tuned to different frequencies. We conclude that marked sensitivity to Schroeder phase is already present at the first CNS processing stage, based on temporal sequence detection across frequency channels rather than on coincidence detection.

A phenomenological spiking model for octopus cells in the posterior\u2013ventral cochlear nucleus

Octopus cells in the posteroventral cochlear nucleus exhibit characteristic onset responses to broad band transients but are little investigated in response to more complex sound stimuli. In this paper, we propose a phenomenological, but biophysically motivated, modeling approach that allows to simulate responses of large populations of octopus cells to arbitrary sound pressure waves. The model depends on only few parameters and reproduces basic physiological characteristics like onset firing and phase locking to amplitude modulations. Simulated responses to speech stimuli suggest that octopus cells are particularly sensitive to high-frequency transients in natural sounds and their sustained firing to phonemes provides a population code for sound level.

KATP and TRPM2-like channels couple metabolic status to resting membrane potential of octopus neurons in the mouse ventral cochlear nucleus

ATP-sensitive potassium (KATP) channels and transient receptor potential melastatin 2 (TRPM2) channels are commonly expressed both pre- and postsynaptically in the central nervous system (CNS). We hypothesized that KATP and TRPM2 may couple metabolic status to the resting membrane potential of octopus neurons of the mouse ventral cochlear nucleus (VCN).Therefore, we studied the expression of KATP channels and TRPM2 channels in octopus cells by immunohistochemical techniques and their contribution to neuronal electrical properties by the electrophysiological patch clamp technique.In immunohistochemical staining of octopus cells, labelling with Kir6.2 and SUR1 antibodies was strong, and labelling with the SUR2 antibody was moderate, but labelling with Kir6.1 was very weak. Octopus cells had intense staining with TRPM2 antibodies.In patch clamp recordings, bath application of KATP channel agonists H2O2 (880 μM), ATZ (1 mM), cromakalim (50 μM), diazoxide (200 μM), NNC 55-0118 and NN 414 separately resulted in hyperpolarizations of resting potential to different extents. Application of 8-Bro-cADPR (50 μM), a specific antagonist of TRPM2 channels, in the presence of H2O2 (880 μM) resulted in further hyperpolarization by approximately 1 mV. The amplitudes of H2O2-induced outward KATP currents and ADPR-induced inward currents were 206.1 ± 31.5 pA (n = 4) and 136.8 ± 22.4 pA, respectively, at rest. Their respective reversal potentials were -77 ± 2.6 mV (n = 3) and -6.3 ± 2.9 (n = 3) and -6.3 ± 2.9 (n = 3).In conclusion, octopus cells appear to possess both KATP channels and TRPM2-like channels. KATP might largely be constituted by SUR1–Kir6.2 subunits and SUR2–Kir6.2 subunits. Both KATP and TRPM2-like channels might have a modulatory action in setting the membrane potential.

Periodicity Pitch Perception.

This study presents a computational model to reproduce the biological dynamics of “listening to music.” A biologically plausible model of periodicity pitch detection is proposed and simulated. Periodicity pitch is computed across a range of the auditory spectrum. Periodicity pitch is detected from subsets of activated auditory nerve fibers (ANFs). These activate connected model octopus cells, which trigger model neurons detecting onsets and offsets; thence model interval-tuned neurons are innervated at the right interval times; and finally, a set of common interval-detecting neurons indicate pitch. Octopus cells rhythmically spike with the pitch periodicity of the sound. Batteries of interval-tuned neurons stopwatch-like measure the inter-spike intervals of the octopus cells by coding interval durations as first spike latencies (FSLs). The FSL-triggered spikes synchronously coincide through a monolayer spiking neural network at the corresponding receiver pitch neurons.

Information Processing by Onset Neurons in the Cat Auditory Brainstem.

Octopus cells in the ventral cochlear nucleus (VCN) have been difficult to study because of the very features that distinguish them from other VCN neurons. We performed in vivo recordings in cats on well-isolated units, some of which were intracellularly labeled and histologically reconstructed. We found that responses to low-frequency tones with frequencies < 1kHz reveal higher levels of neural synchrony and entrainment to the stimulus than the auditory nerve. In responses to higher frequency tones, the neural discharges occur mostly near the stimulus onset. These neurons also respond in a unique way to 100% amplitude-modulated (AM) tones with discharges exhibiting a bandpass tuning. Responses to frequency-modulated sounds (FM) are unusual: Octopus cells react more vigorously during the ascending than the descending parts of the FM stimulus. We examined responses of neurons in the ventral nucleus of the lateral lemniscus (VNLL) whose discharges to tones and AM sounds are similar to octopus cells. Repeated stimulation with short tone pips of VCN and VNLL onset neurons evokes trains of action potentials with gradual shifts toward later times in their first spike latency. This behavior parallels short-term post-synaptic depression observed by other authors in in vitro VCN recordings of octopus cells. VCN and VNLL onset units in cats respond to frozen noise stimuli with gaps as narrow as 1ms with a robust discharge near the stimulus onset following the gap. This finding suggests that VCN and VNLL onset cells play a role in gap detection, which is of great importance to speech perception.

Cost of auditory sharpness: Model-Based estimate of energy use by auditory brainstem “octopus” neurons

Octopus cells (OCs) of the mammalian auditory brainstem precisely encode timing of fast transient sounds and tone onsets. Sharp temporal fidelity of OCs relies on low resting membrane resistance, which suggests high energy expenditure on maintaining ion gradients across plasma membrane. We provide a model-based estimate of energy consumption in resting and spiking OCs. Our results predict that a resting OC consumes up to 2.6 × 109 ATP molecules (ATPs) per second which remarkably exceeds energy consumption of other CNS neurons. Glucose usage by all OCs in the rat is nevertheless low due to their low number. Major part of the OCs energy use results from the ion mechanisms providing for the low membrane resistance: hyperpolarization-activated mixed cation conductance and low-voltage activated K+-conductance. Spatially ordered synapses—a feature of the OCs allowing them to compensate for asynchrony of the synaptic input—brings only a 12% energy saving to OCs excitability cost. Only 13% of total OC energy used for an AP generation (1.5 × 107 ATPs) is associated with the AP generation in the axon initial segment, 64%—with synaptic currents processing and 23%—with keeping resting potential.

Modeling Pitch Perception With an Active Auditory Model Extended by Octopus Cells.

Pitch is an essential category for musical sensations. Models of pitch perception are vividly discussed up to date. Most of them rely on definitions of mathematical methods in the spectral or temporal domain. Our proposed pitch perception model is composed of an active auditory model extended by octopus cells. The active auditory model is the same as used in the Stimulation based on Auditory Modeling (SAM), a successful cochlear implant sound processing strategy extended here by modeling the functional behavior of the octopus cells in the ventral cochlear nucleus and by modeling their connections to the auditory nerve fibers (ANFs). The neurophysiological parameterization of the extended model is fully described in the time domain. The model is based on latency-phase en- and decoding as octopus cells are latency-phase rectifiers in their local receptive fields. Pitch is ubiquitously represented by cascaded firing sweeps of octopus cells. Based on the firing patterns of octopus cells, inter-spike interval histograms can be aggregated, in which the place of the global maximum is assumed to encode the pitch.

Submillisecond Monaural Coincidence Detection by Octopus Cells

Submillisecond Monaural Coincidence Detection by Octopus Cells

Temporal information in tones, broadband noise, and natural vocalizations is conveyed by differential spiking responses in the superior paraolivary nucleus.

Communication sounds across all mammals consist of multiple frequencies repeated in sequence. The onset and offset of vocalizations are potentially important cues for recognizing distinct units, such as phonemes and syllables, which are needed to perceive meaningful communication. The superior paraolivary nucleus (SPON) in the auditory brainstem has been implicated in the processing of rhythmic sounds. Here, we compared how best frequency tones (BFTs), broadband noise (BBN), and natural mouse calls elicit onset and offset spiking in the mouse SPON. The results demonstrate that onset spiking typically occurs in response to BBN, but not BFT stimulation, while spiking at the sound offset occurs for both stimulus types. This effect of stimulus bandwidth on spiking is consistent with two of the established inputs to the SPON from the octopus cells (onset spiking) and medial nucleus of the trapezoid body (offset spiking). Natural mouse calls elicit two main spiking peaks. The first spiking peak, which is weak or absent with BFT stimulation, occurs most consistently during the call envelope, while the second spiking peak occurs at the call offset. This suggests that the combined spiking activity in the SPON elicited by vocalizations reflects the entire envelope, that is, the coarse amplitude waveform. Since the output from the SPON is purely inhibitory, it is speculated that, at the level of the inferior colliculus, the broadly tuned first peak may improve the signal-to-noise ratio of the subsequent, more call frequency-specific peak. Thus, the SPON may provide a dual inhibition mechanism for tracking phonetic boundaries in social-vocal communication.

Compensation for Traveling Wave Delay Through Selection of Dendritic Delays Using Spike-Timing-Dependent Plasticity in a Model of the Auditory Brainstem

Asynchrony among synaptic inputs may prevent a neuron from responding to behaviorally relevant sensory stimuli. For example, “octopus cells” are monaural neurons in the auditory brainstem of mammals that receive input from auditory nerve fibers (ANFs) representing a broad band of sound frequencies. Octopus cells are known to respond with finely timed action potentials at the onset of sounds despite the fact that due to the traveling wave delay in the cochlea, synaptic input from the auditory nerve is temporally diffuse. This paper provides a proof of principle that the octopus cells' dendritic delay may provide compensation for this input asynchrony, and that synaptic weights may be adjusted by a spike-timing dependent plasticity (STDP) learning rule. This paper used a leaky integrate and fire model of an octopus cell modified to include a “rate threshold,” a property that is known to create the appropriate onset response in octopus cells. Repeated audio click stimuli were passed to a realistic auditory nerve model which provided the synaptic input to the octopus cell model. A genetic algorithm was used to find the parameters of the STDP learning rule that reproduced the microscopically observed synaptic connectivity. With these selected parameter values it was shown that the STDP learning rule was capable of adjusting the values of a large number of input synaptic weights, creating a configuration that compensated the traveling wave delay of the cochlea.

Octopus Cells in the Posteroventral Cochlear Nucleus Provide the Main Excitatory Input to the Superior Paraolivary Nucleus.

Auditory streaming enables perception and interpretation of complex acoustic environments that contain competing sound sources. At early stages of central processing, sounds are segregated into separate streams representing attributes that later merge into acoustic objects. Streaming of temporal cues is critical for perceiving vocal communication, such as human speech, but our understanding of circuits that underlie this process is lacking, particularly at subcortical levels. The superior paraolivary nucleus (SPON), a prominent group of inhibitory neurons in the mammalian brainstem, has been implicated in processing temporal information needed for the segmentation of ongoing complex sounds into discrete events. The SPON requires temporally precise and robust excitatory input(s) to convey information about the steep rise in sound amplitude that marks the onset of voiced sound elements. Unfortunately, the sources of excitation to the SPON and the impact of these inputs on the behavior of SPON neurons have yet to be resolved. Using anatomical tract tracing and immunohistochemistry, we identified octopus cells in the contralateral cochlear nucleus (CN) as the primary source of excitatory input to the SPON. Cluster analysis of miniature excitatory events also indicated that the majority of SPON neurons receive one type of excitatory input. Precise octopus cell-driven onset spiking coupled with transient offset spiking make SPON responses well-suited to signal transitions in sound energy contained in vocalizations. Targets of octopus cell projections, including the SPON, are strongly implicated in the processing of temporal sound features, which suggests a common pathway that conveys information critical for perception of complex natural sounds.