Negative self-feedback induces enhancement and transition of spiking activity for class 3 excitability

Post-inhibitory rebound (PIR) spike, which has been widely observed in diverse nervous systems with different physiological functions and simulated in theoretical models with class 2 excitability, presents a counterintuitive nonlinear phenomenon in that the inhibitory effect can facilitate neural firing behavior. In this study, a PIR spike induced by inhibitory stimulation from the resting state corresponding to class 3 excitability that is not related to bifurcation is simulated in the Morris-Lecar neuron. Additionally, the inhibitory self-feedback mediated by an autapse with time delay can evoke tonic/repetitive spiking from phasic/transient spiking. The dynamical mechanism for the PIR spike and the tonic/repetitive spiking is acquired with the phase plane analysis and the shape of the quasi-separatrix curve. The result extends the counterintuitive phenomenon induced by inhibition to class 3 excitability, which presents a potential function of inhibitory autapse and class 3 neuron in many neuronal systems such as the auditory system.

Sensory-thresholded switch of neural firing states in a computational model of the ventromedial hypothalamus

The mouse ventromedial hypothalamus (VMH) is both necessary and sufficient for defensive responses to predator and social threats. Defensive behaviors typically involve cautious approach toward potentially threatening stimuli aimed at obtaining information about the risk involved, followed by sudden avoidance and flight behavior to escape harm. In vivo neural recording studies in mice have identified two major populations of VMH neurons that either increase their firing activity as the animal approaches the threat (called Assessment+ cells) or increase their activity as the animal flees the threat (called Flight+ cells). Interestingly, Assessment+ and Flight+ cells abruptly decrease and increase their firing activity, respectively, at the decision point for flight, creating an escape-related “switch” in functional state. This suggests that the activity of the two cell types in VMH is coordinated and could result from local circuit interactions. Here, we used computational modelling to test if a local inhibitory feedback circuit could give rise to key features of the neural activity seen in VMH during the approach-to-flight transition. Starting from a simple dual-population inhibitory feedback circuit receiving repeated trains of monotonically increasing sensory input to mimic approach to threat, we tested the requirement for balanced sensory input, balanced feedback, short-term synaptic plasticity, rebound excitation, and inhibitory feedback exclusivity to reproduce an abrupt, sensory-thresholded reciprocal firing change that resembles Assessment+ and Flight+ cell activity seen in vivo. Our work demonstrates that a relatively simple local circuit architecture is sufficient for the emergence of firing patterns similar to those seen in vivo and suggests that a reiterative process of experimental and computational work may be a fruitful avenue for better understanding the functional organization of mammalian instinctive behaviors at the circuit level.

A Model for Estimating Tactile Sensation by Machine Learning Based on Vibration Information Obtained while Touching an Object

The tactile sensation is an important indicator of the added value of a product, and it is thus important to be able to evaluate this sensation quantitatively. Sensory evaluation is generally used to quantitatively evaluate the tactile sensation of an object. However, statistical evaluation of the tactile sensation requires many participants and is, thus, time-consuming and costly. Therefore, tactile sensing technology, as opposed to sensory evaluation, is attracting attention. In establishing tactile sensing technology, it is necessary to estimate the tactile sensation of an object from information obtained by a tactile sensor. In this research, we developed a tactile sensor made of two-layer silicone rubber with two strain gauges in each layer and obtained vibration information as the sensor traced an object. We then extracted features from the vibration information using deep autoencoders, following the nature of feature extraction by neural firing due to vibrations perceived within human fingers. We also conducted sensory evaluation to obtain tactile scores for different words from participants. We finally developed a tactile sensation estimation model for each of the seven samples and evaluated the accuracy of estimating the tactile sensation of unknown samples. We demonstrated that the developed model can properly estimate the tactile sensation for at least four of the seven samples.

Multiple and Complex Codimension-2 Bifurcations underlying Post-inhibitory Rebound Spike and Excitability Transition

Neuron exhibits nonlinear dynamics such as excitability transition and post-inhibitory rebound (PIR) spike related to bifurcations, which are associated with information processing, locomotor modulation, or brain disease. PIR spike is evoked by inhibitory stimulation instead of excitatory stimulation, which presents a challenge to the threshold concept. In the present paper, 7 codimension-2 or degenerate bifurcations related to 10 codimension-1 bifurcations are acquired in a neuronal model, which presents the bifurcations underlying the excitability transition and PIR spike. Type I excitability corresponds to saddle-node bifurcation on an invariant cycle (SNIC) bifurcation, and type II excitability to saddle-node (SN) bifurcation or sub-critical Hopf (SubH) bifurcation or sup-critical Hopf (SupH) bifurcation. The excitability transition from type I to II corresponds to the codimension-2 bifurcation, Saddle-Node Homoclinic orbit (SNHO) bifurcation, via which SNIC bifurcation terminates and meanwhile big homoclinic orbit (BHom) bifurcation and SN bifurcation emerge. A degenerate bifurcation via which BHom bifurcation terminates and fold limit cycle (LPC) bifurcation emerges is responsible for spiking transition from type I to II, and the roles of other codimension-2 bifurcations (Cusp, Bogdanov-Takens, and Bautin) are discussed. In addition, different from the widely accepted viewpoint that PIR spike is mainly evoked near Hopf bifurcation rather than SNIC bifurcation, PIR spike is identified to be induced near SNIC or BHom or LPC bifurcations, and threshold curves resemble that of Hopf bifurcation. The complex bifurcations present comprehensive and deep understandings of excitability transition and PIR spike, which are helpful for the modulation to neural firing activities and physiological functions.

Electrophysiological investigation of intact retina with soft printed organic neural interface

Objective. Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities. Ex vivo, the retina can be readily investigated using multi electrode arrays. However, multi electrode array recording and stimulation from an intact retina (in the eye) has been so far insufficient. Approach. In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20 µm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40 µm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50 µm) PU film. Plasma polymerized EDOT was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both ex-planted and intact inside an enucleated eye, were used. Main results. A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate. Ex vivo electrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed. Significance. Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissue in vivo.

Long-term stability of neural activity in the motor system

How established behaviors are retained and stably produced by a nervous system in constant flux remains a mystery. One possible solution is to fix the activity patterns of single neurons in the relevant circuits. Alternatively, activity in these circuits could change over time, provided that the network dynamics are contained within a manifold that produces stable behavior. To arbitrate between these possibilities, we recorded single unit activity in motor cortex and striatum continuously for several months as rats performed stereotyped motor behaviors - both learned and innate. We found long-term stability in behaviorally locked single neuron activity patterns across both brain regions. A small amount of neural drift observed over weeks of recording could be explained by concomitant changes in task-irrelevant behavioral output and the stochasticity of neural firing. These results suggest that stereotyped behaviors are stored and generated in stable neural circuits.

Identification of SSRI-evoked antidepressant sensory signals by decoding vagus nerve activity

The vagus nerve relays mood-altering signals originating in the gut lumen to the brain. In mice, an intact vagus is required to mediate the behavioural effects of both intraluminally applied selective serotonin reuptake inhibitors and a strain of Lactobacillus with antidepressant-like activity. Similarly, the prodepressant effect of lipopolysaccharide is vagus nerve dependent. Single vagal fibres are broadly tuned to respond by excitation to both anti- and prodepressant agents, but it remains unclear how neural responses encode behaviour-specific information. Here we demonstrate using ex vivo experiments that for single vagal fibres within the mesenteric neurovascular bundle supplying the mouse small intestine, a unique neural firing pattern code is common to both chemical and bacterial vagus-dependent antidepressant luminal stimuli. This code is qualitatively and statistically discernible from that evoked by lipopolysaccharide, a non-vagus-dependent antidepressant or control non-antidepressant Lactobacillus strain and are not affected by sex status. We found that all vagus dependent antidepressants evoked a decrease in mean spike interval, increase in spike burst duration, decrease in gap duration between bursts and increase in intra-burst spike intervals. Our results offer a novel neuronal electrical perspective as one explanation for mechanisms of action of gut-derived vagal dependent antidepressants. We expect that our ex vivo individual vagal fibre recording model will improve the design and operation of new, extant electroceutical vagal stimulation devices currently used to treat major depression. Furthermore, use of this vagal antidepressant code should provide a valuable screening tool for novel potential oral antidepressant candidates in preclinical animal models.

Neural Burst Firing and Its Roles in Mental and Neurological Disorders

Neural firing patterns are critical for specific information coding and transmission, and abnormal firing is implicated in a series of neural pathologies. Recent studies have indicated that enhanced burst firing mediated by T-type voltage-gated calcium channels (T-VGCCs) in specific neuronal subtypes is involved in several mental or neurological disorders such as depression and epilepsy, while suppression of T-VGCCs relieve related symptoms. Burst firing consists of groups of relatively high-frequency spikes separated by quiescence. Neurons in a variety of brain areas, including the thalamus, hypothalamus, cortex, and hippocampus, display burst firing, but the ionic mechanisms that generating burst firing and the related physiological functions vary among regions. In this review, we summarize recent findings on the mechanisms underlying burst firing in various brain areas, as well as the roles of burst firing in several mental and neurological disorders. We also discuss the ion channels and receptors that may regulate burst firing directly or indirectly, with these molecules highlighted as potential intervention targets for the treatment of mental and neurological disorders.

Insights into the evolutionary origin of the pineal color discrimination mechanism from the river lamprey

Background Pineal-related organs in cyclostomes, teleosts, amphibians, and reptiles exhibit color opponency, generating antagonistic neural responses to different wavelengths of light and thereby sensory information about its “color”. Our previous studies suggested that in zebrafish and iguana pineal-related organs, a single photoreceptor cell expressing both UV-sensitive parapinopsin and green-sensitive parietopsin generates color opponency in a “one-cell system.” However, it remains unknown to what degree these opsins and the single cell-based mechanism in the pineal color opponency are conserved throughout non-mammalian vertebrates. Results We found that in the lamprey pineal organ, the two opsins are conserved but that, in contrast to the situation in other vertebrate pineal-related organs, they are expressed in separate photoreceptor cells. Intracellular electrophysiological recordings demonstrated that the parietopsin-expressing photoreceptor cells with Go-type G protein evoke a depolarizing response to visible light. Additionally, spectroscopic analyses revealed that parietopsin with 11-cis 3-dehydroretinal has an absorption maximum at ~570 nm, which is in approximate agreement with the wavelength (~560 nm) that produces the maximum rate of neural firing in pineal ganglion cells exposed to visible light. The vesicular glutamate transporter is localized at both the parietopsin- and parapinopsin-expressing photoreceptor terminals, suggesting that both types of photoreceptor cells use glutamate as a transmitter. Retrograde tracing of the pineal ganglion cells revealed that the terminal of the parietopsin-expressing cells is located close enough to form a neural connection with the ganglion cells, which is similar to our previous observation for the parapinopsin-expressing photoreceptor cells and the ganglion cells. In sum, our observations point to a “two-cell system” in which parietopsin and parapinopsin, expressed separately in two different types of photoreceptor cells, contribute to the generation of color opponency in the pineal ganglion cells. Conclusion Our results indicate that the jawless vertebrate, lamprey, employs a system for color opponency that differes from that described previously in jawed vertebrates. From a physiological viewpoint, we propose an evolutionary insight, the emergence of pineal “one-cell system” from the ancestral “multiple (two)-cell system,” showing the opposite evolutionary direction to that of the ocular color opponency.

Orthogonal representation of task-related information in theta phase-based multiple place fields of single units in the subiculum

The subiculum is positioned at a critical juncture at the interface of the hippocampus with the rest of the brain. However, the exact roles of the subiculum in most hippocampal-dependent memory tasks remain largely unknown. One obstacle to make analytical comparisons of neural firing patterns between the subiculum and hippocampal CA1 is the broad firing fields of the subicular cells. Here, we used spiking phases in relation to theta rhythm to parse the broad firing field of a subicular neuron into multiple subfields to find the unique functional contribution of the subiculum while male rats performed a hippocampal-dependent visual scene memory task. Some of the broad firing fields of the subicular neurons were successfully divided into multiple subfields by using the theta-phase precession cycle. The resulting phase-based fields in the subiculum were more similar to those in CA1 in terms of the field size and phase-precession strength. The new method significantly improved the detection of task-relevant information in subicular cells without affecting the information content represented by CA1 cells. Notably, multiple fields of a single subicular neuron, unlike those in the CA1, could carry heterogeneous task-related information such as visual context and choice response. Our findings suggest that the subicular cells integrate multiple task-related factors by using theta rhythm to associate environmental context with action.