Mathematical models of cochlear nucleus onset neurons: II. model with dynamic spike-blocking state

Onset (On) neurons in the cochlear nucleus (CN), characterized by their prominent response to the onset followed by little or no response to the steady-state of sustained stimuli, have a remarkable ability to entrain (firing 1 spike per cycle of a periodic stimulus) to low-frequency tones up to 1000 Hz. In this article, we present a point-neuron model with independent, excitatory auditory-nerve (AN) inputs that accounts for the ability of On neurons to both produce onset responses for high-frequency tone bursts and entrain to a wide range of low-frequency tones. With a fixed-duration spike-blocking state after a spike (an absolute refractory period), the model produces entrainment to a broad range of low-frequency tones and an On response with short interspike intervals (chopping) for high-frequency tone bursts. To produce On response patterns with no chopping, we introduce a novel, more complex, active membrane model in which the spike-blocking state is maintained until the instantaneous membrane voltage falls below a transition voltage. During the sustained depolarization for a high-frequency tone burst, the new model does not chop because it enters a spike-blocking state after the first spike and fails to leave this state until the membrane voltage returns toward rest at the end of the stimulus. The model entrains to low-frequency tones because the membrane voltage falls below the transition voltage on every cycle when the AN inputs are phase-locked. With the complex membrane model, On response patterns having moderate steady-state activity for high-frequency tone bursts (On-L) are distinguished from those having no steady-state activity (On-I) by requiring fewer AN inputs. Voltage-gated ion channels found in On-responding neurons of the CN may underlie the hypothesized dynamic spike-blocking state. These results provide a mechanistic rationale for distinguishing between the different physiological classes of CN On neurons.     

Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus

Biphasic neural response properties, where the optimal stimulus for driving a neural response changes from one stimulus pattern to the opposite stimulus pattern over short periods of time, have been described in several visual areas, including lateral geniculate nucleus (LGN), primary visual cortex (V1), and middle temporal area (MT). We describe a hierarchical model of predictive coding and simulations that capture these temporal variations in neuronal response properties. We focus on the LGN-V1 circuit and find that after training on natural images the model exhibits the brain's LGN-V1 connectivity structure, in which the structure of V1 receptive fields is linked to the spatial alignment and properties of center-surround cells in the LGN. In addition, the spatio-temporal response profile of LGN model neurons is biphasic in structure, resembling the biphasic response structure of neurons in cat LGN. Moreover, the model displays a specific pattern of influence of feedback, where LGN receptive fields that are aligned over a simple cell receptive field zone of the same polarity decrease their responses while neurons of opposite polarity increase their responses with feedback. This phase-reversed pattern of influence was recently observed in neurophysiology. These results corroborate the idea that predictive feedback is a general coding strategy in the brain.     

Functional evidence for a dual route to amygdala

The amygdala plays a central role in evaluating the behavioral importance of sensory information. Anatomical subcortical pathways provide direct input to the amygdala from early sensory systems and may support an adaptively valuable rapid appraisal of salient information. However, the functional significance of these subcortical inputs remains controversial. We recorded magnetoencephalographic activity evoked by tones in the context of emotionally valent faces and tested two competing biologically motivated dynamic causal models against these data: the dual and cortical models. The dual model comprised two parallel (cortical and subcortical) routes to the amygdala, whereas the cortical model excluded the subcortical path. We found that neuronal responses elicited by salient information were better explained when a subcortical pathway was included. In keeping with its putative functional role of rapid stimulus appraisal, the subcortical pathway was most important early in stimulus processing. However, as often assumed, its action was not limited to the context of fear, pointing to a more widespread information processing role. Thus, our data supports the idea that an expedited evaluation of sensory input is best explained by an architecture that involves a subcortical path to the amygdala.     

Mathematical models of cochlear nucleus onset neurons: I. Point neuron with many weak synaptic inputs

The cochlear nucleus (CN) presents a unique opportunity for quantitatively studying input-output transformations by neurons because it gives rise to a variety of different response types from a relatively homogeneous input source, the auditory nerve (AN). Particularly interesting among CN neurons are Onset (On) neurons, which have a prominent response to the onset of sustained sounds followed by little or no response in the steady-state. On neurons contrast sharply with their AN inputs, which respond vigorously throughout stimuli. On neurons can entrain to stimuli (firing once per cycle of a periodic stimulus) at up to 1000 Hz, unlike their AN inputs. To understand the mechanisms underlying these response patterns, we tested whether an integrate-to-threshold point-neuron model with a fixed refractory period can account for On discharge patterns for tones, systematically examining the effect of membrane time constant and the number and strength of the exclusively excitatory AN synaptic inputs. To produce both onset responses to high-frequency tone bursts and entrainment to a broad range of low-frequency tones, the model must have a short time constant (0.125 ms) and a large number (>100) of weak synaptic inputs, properties that are consistent with the electrical properties and anatomy of On-responding cells. With these parameters, the model acts like a coincidence detector with a threshold-like relationship between the instantaneous discharge rates of the output and the inputs. Onset responses to high-frequency tone bursts result because the threshold effect enhances the initial response of the AN inputs and suppresses their relatively lower sustained response. However, when the model entrains across a broad range of frequencies, it also produces short interspike intervals at the onset of high-frequency tone bursts, a response pattern not found in all types of On neurons. These results show a tradeoff, that may be a general property of many neurons, between following rapid stimulus fluctuations and responding without short interspike intervals at the onset of sustained stimuli.     

Cerebellum,temporal predictability and the updating of a mental model

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form (‘what’) and stimulus occurrence (‘when’). Consequently, behaviour is optimal when we can anticipate both the ‘what’ and ‘when’ dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention.     

Modeling inhibition of type II units in the dorsal cochlear nucleus

 Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous but nonmonotonic responses to best frequency tones as a function of sound pressure level, and relatively weak responses to noise. A model of DCN neural circuitry was used to explore two hypothetical mechanisms by which neurons may be endowed with type II unit response properties. Both mechanisms assume that type II units receive excitatory input from auditory nerve (AN) fibers and inhibitory input from an unspecified class of cochlear nucleus interneurons that also receive excitatory AN input. The first mechanism, a lateral inhibition (LI) model, supposes that type II units receive inhibitory input from a number of narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type II unit. Tonal stimuli near BF result in only weak inhibitory input, but broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II unit response. The second mechanism, a wideband inhibition (WBI) model, supposes that type II units receive inhibitory input from interneurons that are broadly tuned so that they respond more vigorously to broadband stimuli than to tones. Physiological and anatomical evidence points to the possible existence of such a class of neurons in the cochlear nucleus. The model extends an earlier computer model of an iso-frequency DCN patch to multiple frequency slices and adds a population of interneurons to provide the inhibition to model type II units (called I2-cells). The results show that both mechanisms accurately simulate responses of type II units to tones and noise. An experimental paradigm for distinguishing the two mechanisms is proposed. Received: 30 December 1996/Accepted in revised form: 13 March 1997     

Adaptation to stimulus contrast and correlations during natural visual stimulation

In this study, we characterize the adaptation of neurons in the cat lateral geniculate nucleus to changes in stimulus contrast and correlations. By comparing responses to high- and low-contrast natural scene movie and white noise stimuli, we show that an increase in contrast or correlations results in receptive fields with faster temporal dynamics and stronger antagonistic surrounds, as well as decreases in gain and selectivity. We also observe contrast- and correlation-induced changes in the reliability and sparseness of neural responses. We find that reliability is determined primarily by processing in the receptive field (the effective contrast of the stimulus), while sparseness is determined by the interactions between several functional properties. These results reveal a number of adaptive phenomena and suggest that adaptation to stimulus contrast and correlations may play an important role in visual coding in a dynamic natural environment.     

Enhancement and Distortion in the Temporal Representation of Sounds in the Ventral Cochlear Nucleus of Chinchillas and Cats

A subset of neurons in the cochlear nucleus (CN) of the auditory brainstem has the ability to enhance the auditory nerve''s temporal representation of stimulating sounds. These neurons reside in the ventral region of the CN (VCN) and are usually known as highly synchronized, or high-sync, neurons. Most published reports about the existence and properties of high-sync neurons are based on recordings performed on a VCN output tract—not the VCN itself—of cats. In other species, comprehensive studies detailing the properties of high-sync neurons, or even acknowledging their existence, are missing.Examination of the responses of a population of VCN neurons in chinchillas revealed that a subset of those neurons have temporal properties similar to high-sync neurons in the cat. Phase locking and entrainment—the ability of a neuron to fire action potentials at a certain stimulus phase and at almost every stimulus period, respectively—have similar maximum values in cats and chinchillas. Ranges of characteristic frequencies for high-sync neurons in chinchillas and cats extend up to 600 and 1000 Hz, respectively. Enhancement of temporal processing relative to auditory nerve fibers (ANFs), which has been shown previously in cats using tonal and white-noise stimuli, is also demonstrated here in the responses of VCN neurons to synthetic and spoken vowel sounds.Along with the large amount of phase locking displayed by some VCN neurons there occurs a deterioration in the spectral representation of the stimuli (tones or vowels). High-sync neurons exhibit a greater distortion in their responses to tones or vowels than do other types of VCN neurons and auditory nerve fibers.Standard deviations of first-spike latency measured in responses of high-sync neurons are lower than similar values measured in ANFs'' responses. This might indicate a role of high-sync neurons in other tasks beyond sound localization.     

Neural organization and responses to complex stimuli in the dorsal cochlear nucleus.

The dorsal division of the cochlear nucleus (DCN) is the most complex of its subdivisions in terms of both anatomical organization and physiological response types. Hypotheses about the functional role of the DCN in hearing are as yet primitive, in part because the organizational complexity of the DCN has made development of a comprehensive and predictive model of its input-output processing difficult. The responses of DCN cells to complex stimuli, especially filtered noise, are interesting because they demonstrate properties that cannot be predicted, without further assumptions, from responses to narrow band stimuli, such as tones. In this paper, we discuss the functional organization of the DCN, i.e. the morphological organization of synaptic connections within the nucleus and the nature of synaptic interactions between its cells. We then discuss the responses of DCN principal cells to filtered noise stimuli that model the spectral sound localization cues produced by the pinna. These data imply that the DCN plays a role in interpreting sound localization cues; supporting evidence for such a role is discussed.     

Neural representation of the acoustic biotope

Cats were stimulated with tones and with natural sounds selected from the normal acoustic environment of the animal. Neural activity evoked by the natural sounds and tones was recorded in the cochlear nucleus and in the medial geniculate body. The set of biological sounds proved to be effective in influencing neural activity of single cells at both levels in the auditory system. At the level of the cochlear nucleus the response of a neuron evoked by a natural sound stimulus could be understood reasonably well on the basis of the structure of the spectrograms of the natural sounds and the unit's responses to tones. At the level of the medial geniculate body analysis with tones did not provide sufficient information to explain the responses to natural sounds. At this level the use of an ensemble of natural sound stimuli allows the investigation of neural properties, which are not seen by analysis with simple artificial stimuli. Guidelines for the construction of an ensemble of complex natural sound stimuli, based on the ecology and ethology of the animal under investigation are discussed. This stimulus ensemble is defined as the Acoustic Biotope.     

Unit responses in area 5b of the suprasylvian gyrus to stimulation of the ventral posterolateral thalamic nucleus

Unanesthetized cats were immobilized with D-tubocurarine. Single unit responses in area 5b of the suprasylvian gyrus to stimulation of the ventral posterolateral thalamic nucleus were recorded extracellularly. Of the total number of neurons tested, 32% were excited and 3% inhibited. In 65% of neurons the responses were mixed, most of them being predominantly excitatory. Repetitive stimulation of the ventral posterolateral nucleus (6–9/sec) frequently intensified the excitatory component of the responses. Sometimes inhibition, present in the response to a single stimulus, was replaced by increased excitation. However, the same response as to a single stimulus frequently appeared in response to each consecutive stimulus of a series. Stimulation of the ventral posterolateral nucleus had a mainly excitatory effect on neurons in area 5b. Stimulation of the dorsal lateral nucleus, on the other hand, inhibited their activity. This antagonism could also be observed on the same neuron. It was concluded from the short latent periods of the orthodromic responses (3–6 msec) and from the antidromic responses of the cortical neurons to stimulation of the ventral posterolateral nucleus that this nucleus has direct two-way connections with the cortex of area 5b.     

Stimulus-specific adaptation and deviance detection in the rat auditory cortex

Stimulus-specific adaptation (SSA) is the specific decrease in the response to a frequent ('standard') stimulus, which does not generalize, or generalizes only partially, to another, rare stimulus ('deviant'). Stimulus-specific adaptation could result simply from the depression of the responses to the standard. Alternatively, there may be an increase in the responses to the deviant stimulus due to the violation of expectations set by the standard, indicating the presence of true deviance detection. We studied SSA in the auditory cortex of halothane-anesthetized rats, recording local field potentials and multi-unit activity. We tested the responses to pure tones of one frequency when embedded in sequences that differed from each other in the frequency and probability of the tones composing them. The responses to tones of the same frequency were larger when deviant than when standard, even with inter-stimulus time intervals of almost 2 seconds. Thus, SSA is present and strong in rat auditory cortex. SSA was present even when the frequency difference between deviants and standards was as small as 10%, substantially smaller than the typical width of cortical tuning curves, revealing hyper-resolution in frequency. Strong responses were evoked also by a rare tone presented by itself, and by rare tones presented as part of a sequence of many widely spaced frequencies. On the other hand, when presented within a sequence of narrowly spaced frequencies, the responses to a tone, even when rare, were smaller. A model of SSA that included only adaptation of the responses in narrow frequency channels predicted responses to the deviants that were substantially smaller than the observed ones. Thus, the response to a deviant is at least partially due to the change it represents relative to the regularity set by the standard tone, indicating the presence of true deviance detection in rat auditory cortex.     

Orientation sensitive properties of visually driven neurons in extrastriate area 21a of cat cortex

Orientation sensitive properties of extrastriate area 21a neurons were investigated. Special attention was paid to the qualitative characteristics of neuron responses to the different orientations of visual stimulus motion across neuron classical receptive fields (CRF). The results of experiments have shown that a group of neurons (31%) in area 21a with specialized responses to moving visual stimuli changed their direction selective (DS) characteristics depending on the orientation of the stimulus movement. Some neurons reveal an abrupt drop of the direction sensitivity index (DI) to certain orientation (58%), and some show significant increase of DI at one of applied orientations of stimulus motion (22%). Detailed investigation of response patterns of non-directional neurons to different orientations of stimulus motion have revealed clear-cut qualitative differences, such as different regularities in the distribution of inter-peak inhibitory intervals in the response pattern in dependence of the orientation of stimulus motion. The investigation of neuron CRF stationary functional organization did not reveal correlations between RF's spatial functional organization, and that of qualitative modulations of neuron response patterns. A suggestion was put forward, that visual information central processing of orientation discrimination is a complex integrative process that includes quantitative as well as qualitative transformations of neuron activity.     

A simulation of chopper neurons in the cochlear nucleus with wideband input from onset neurons

The unique temporal and spectral properties of chopper neurons in the cochlear nucleus cannot be fully explained by current popular models. A new model of sustained chopper neurons was therefore suggested based on the assumption that chopper neurons receive input both from onset neurons and the auditory nerve (Bahmer and Langner in Biol Cybern 95:4, 2006). As a result of the interaction of broadband input from onset neurons and narrowband input from the auditory nerve, the chopper neurons in our model are characterized by a remarkable combination of sharp frequency tuning to pure tones and faithful periodicity coding. Our simulations show that the width of the spectral integration of the onset neuron is crucial for both the precision of periodicity coding and their resolution of single components of sinusoidally amplitude-modulated sine waves. One may hypothesize, therefore, that it would be an advantage if the hearing system were able to adapt the spectral integration of onset neurons to varying stimulus conditions.     

Mechanisms of cardiac cell excitation with premature monophasic and biphasic field stimuli: a model study.

The mechanisms by which extracellular electric field stimuli induce the (re)excitation of cardiac cells in various stages of refractoriness are still not well understood. We modeled the interactions between an isolated cardiac cell and imposed extracellular electric fields to determine the mechanisms by which relatively low-strength uniform monophasic and biphasic field stimuli induce premature reexcitations. An idealized ventricular cell was simulated with 11 subcellular membrane patches, each of which obeyed Luo-Rudy (phase 1) kinetics. Implementing a standard S1-S2 pulse protocol, strength-interval maps of the cellular excitatory responses were generated for rectangular monophasic and symmetric biphasic field stimuli of 2, 5, 10, and 20 ms total duration. In contrast to previously documented current injection studies, our results demonstrate that a cardiac cell exhibits a significantly nonmonotonic excitatory response to premature monophasic and, to a much lesser degree, biphasic field stimuli. Furthermore, for monophasic stimuli at low field strengths, the cell is exquisitely sensitive to the timing of the shock, demonstrating a classic all-or-none depolarizing response. However, at higher field strengths this all-or-none sensitivity reverts to a more gradual transition of excitatory responses with respect to stimulus prematurity. In contrast, biphasic stimuli produce such graded responses at all suprathreshold stimulus strengths. Similar behaviors are demonstrated at all S2 stimulus durations tested. The generation of depolarizing (sodium) currents is triggered by one or more of the sharp field gradient changes produced at the stimulus edges-i.e., make, break, and transphasic (for biphasic stimuli)-with the magnitude of these edge-induced current contributions dependent on both the prematurity and the strength of the applied field. In all cases, however, depolarizing current arises from the partial removal of sodium inactivation from at least part of the cell, because of either the natural process of repolarization or a localized acceleration of this process by the impressed field.     

Neural mechanism of dynamic responses of neurons in inferior temporal cortex in face perception

Understanding the neural mechanisms of object and face recognition is one of the fundamental challenges of visual neuroscience. The neurons in inferior temporal (IT) cortex have been reported to exhibit dynamic responses to face stimuli. However, little is known about how the dynamic properties of IT neurons emerge in the face information processing. To address this issue, we made a model of IT cortex, which performs face perception via an interaction between different IT networks. The model was based on the face information processed by three resolution maps in early visual areas. The network model of IT cortex consists of four kinds of networks, in which the information about a whole face is combined with the information about its face parts and their arrangements. We show here that the learning of face stimuli makes the functional connections between these IT networks, causing a high spike correlation of IT neuron pairs. A dynamic property of subthreshold membrane potential of IT neuron, produced by Hodgkin–Huxley model, enables the coordination of temporal information without changing the firing rate, providing the basis of the mechanism underlying face perception. We show also that the hierarchical processing of face information allows IT cortex to perform a “coarse-to-fine” processing of face information. The results presented here seem to be compatible with experimental data about dynamic properties of IT neurons.     

Neuronal correlates of the activation of the brain-reinforcing system in dogs

In analysis of neuronal activity of g. proreus of dogs brain in response to positive and differentiation conditioned cutaneous stimuli, in 44% of 78 studied neurons "late responses" appeared in the form of impulse activity intensification elicited by a positive conditioned stimulus after the end of eating and by a differentiation one--during conditioned signal action; it persisted in different neurones for 30--60 s. By means of various functional tests it has been shown that these reactions are a neurophysiological correlate of animals emotional state gradient.     

Frequency-invariant representation of interaural time differences in mammals

Interaural time differences (ITDs) are the major cue for localizing low-frequency sounds. The activity of neuronal populations in the brainstem encodes ITDs with an exquisite temporal acuity of about 10 μs. The response of single neurons, however, also changes with other stimulus properties like the spectral composition of sound. The influence of stimulus frequency is very different across neurons and thus it is unclear how ITDs are encoded independently of stimulus frequency by populations of neurons. Here we fitted a statistical model to single-cell rate responses of the dorsal nucleus of the lateral lemniscus. The model was used to evaluate the impact of single-cell response characteristics on the frequency-invariant mutual information between rate response and ITD. We found a rough correspondence between the measured cell characteristics and those predicted by computing mutual information. Furthermore, we studied two readout mechanisms, a linear classifier and a two-channel rate difference decoder. The latter turned out to be better suited to decode the population patterns obtained from the fitted model.     

Feedforward origins of response variability underlying contrast invariant orientation tuning in cat visual cortex

Contrast invariant orientation tuning in simple cells of the visual cortex depends critically on contrast dependent trial-to-trial variability in their membrane potential responses. This observation raises the question of whether this variability originates from within the cortical circuit or the feedforward inputs from the lateral geniculate nucleus (LGN). To distinguish between these two sources of variability, we first measured membrane potential responses while inactivating the surrounding cortex, and found that response variability was nearly unaffected. We then studied variability in the LGN, including contrast dependence, and the trial-to-trial correlation in responses between nearby neurons. Variability decreased significantly with contrast, whereas correlation changed little. When these experimentally measured parameters of variability were applied to a feedforward model of simple cells that included realistic mechanisms of synaptic integration, contrast-dependent, orientation independent variability emerged in the membrane potential responses. Analogous mechanisms might contribute to the stimulus dependence and propagation of variability throughout the neocortex.     

Bicuculline对小鼠中脑下丘听神经元

采用微电泳技术考察了GABAA受体拮抗剂荷包牡丹碱（bicuculline）,对小鼠中脑下丘听神经元强度-放电率曲线、频率调谐曲线和听空间反应域的影响。结果表明,微电泳bicuculline使听神经元的放电率显著提高,多数神经元的强度-放电率曲线变为单调型;听神经元频率调谐曲线加宽,并且对曲线上部的作用更加明显;听神经元的听空间反应域增大,方向敏感性降低。实验结果提示了GABA能抑制在下丘听信息处理中的重要作用。