Biology subjects

Kozlov, A. S.

Publications and source records attributed to Kozlov, A. S..

9 recordsLinked to original sources

bioRxiv2025

Astrocytes and neurons encode natural stimuli with partially shared but distinct composite receptive fields

Astrocytes are increasingly recognized as active participants in sensory processing, but whether they show selective responses to stimulus features, analogous to neuronal receptive fields, is not yet established. To address this, we used two-photon calcium imaging in the auditory cortex of anesthetized mice during presentation of natural ultrasonic vocalizations. Our aim was to compare astrocytic responses with those of neighboring neurons and to determine whether astrocytes exhibit feature-selective receptive fields. Event detection showed that astrocytic calcium activity is highly heterogeneous, but only a minority of events were consistently stimulus-linked. To examine this stimulus-driven subset, we estimated receptive field features using maximum noise entropy modeling and compared them with those of concurrently recorded neurons. Despite qualitative similarities in receptive-field features, analysis of modulation spectra and principal angles showed that astrocytic and neuronal receptive fields overlap but occupy distinct regions of feature space. This indicates that astrocytes and neurons encode partially shared, but not identical, dimensions of the sensory stimulus. Our findings indicate that astrocytes encode diverse sensory features, providing an additional contribution to neuronal encoding. This suggests that astrocytic calcium activity is not simply a reflection of neuronal firing, but instead represents a distinct component of cortical sensory processing. New and noteworthyWe used two-photon imaging to record calcium activity in astrocytes and neighboring neurons during presentation of natural ultrasonic vocalizations. We show that astrocyte activity is highly heterogeneous across spatial and temporal scales. Further analyses indicate that a subset of astrocyte calcium activity is stimulus-linked and encodes dimensions of the stimulus that partially overlap but are not identical to those encoded by neurons.

neuroscience↗

bioRxiv2025

A Geometrically Transient Material for Bioelectronic Implants

The outstanding barrier properties of skin make it difficult to obtain reliable physiological information (especially chemical) without the use of implantable bioelectronic sensing devices to directly access the internal biology. The clinical utility of bioelectronic implants however, hinges on a key geometrical optimization problem: devices must scale-down in size to reduce surgical invasiveness while also creating enough space to integrate electronics for wireless power delivery, data exchange, and electrical/electrochemical monitoring. Here, we present a minimally invasive bioelectronic implant with a transient geometry that can be inserted subcutaneously and measures important markers, such as pH, temperature, cardiac and respiratory activity, and levels of lithium, an important element for medical applications. To produce this new class of minimally invasive and foldable implantable sensors, we developed a fabrication method that works with highly flexible substrates to enable multiple-fold miniaturization during implantation. After implantation, the implant autonomously unfolds back to its planar form for continuous wireless operation. We demonstrate the key concepts concerning implantation, operation, and removal through extensive in vitro, ex vivo, and in vivo animal experiments. Our approach allows for robust multiplexed monitoring using quick and suture-free insertion procedures and may provide a unique advantage in the transition towards personalized health profiles.

bioengineering↗

bioRxiv2024

Alterations in topology, cost and dynamics of gamma-band EEG functional networks in a preclinical model of traumatic brain injury

Traumatic brain injury is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including post-traumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band using a preclinical model of blast-induced traumatic brain injury over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared to age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying cost of spatially embedded networks that controls for connectivity strength differences, and suggest metabolic drivers as a candidate for the observed differences. Furthermore, we employed a brain-wide computational model of seizure dynamics and attribute brain reorganization to a homeostatic mechanism of activity regulation with the potential unintended consequence of driving generalized seizures. Finally, we demonstrated post-injury hyperexcitability that manifests as an increase in sound-evoked response amplitudes at the cortical level. Our work characterizes for the first time gamma-band functional network reorganization in a model of brain injury and proposes potential causes of these changes, thus identifying targets for future therapeutic interventions.

neuroscience↗

bioRxiv2024

Flexible integration of natural stimuli by auditory cortical neurons

Neurons have rich input-output functions for processing and combining their inputs. Although many experiments characterize these functions by directly activating synaptic inputs on dendrites in vitro, the integration of spatiotemporal inputs representing real-world stimuli is less well studied. Using ethologically relevant stimuli, we study neuronal integration in relation to Boolean AND and OR operations thought to be important for pattern recognition. We recorded single-unit responses in the mouse auditory cortex to pairs of ultrasonic mouse vocalization (USV) syllables. We observed a range of integration responses, spanning the sublinear to supralinear regimes, with many responses resembling the MAX-like function, an instantiation of the OR operation. Integration was more MAX-like for strongly activating features, and more AND-like for spectrally distinct inputs. Importantly, single neurons could implement more than one integration function, in contrast to artificial networks which typically fix activation functions across all units and inputs. To understand the mechanism underlying the flexibility and heterogeneity in neuronal integration, we modelled how dendritic properties could influence the integration of inputs with complex spectrotemporal structure. Our results link nonlinear integration in dendrites to single-neuron computations for pattern recognition. Significance statementSensory neurons compute over their inputs, combining them in ways to achieve selectivity and invariance for pattern recognition. Using real-world stimuli, we show that single cortical neurons are flexible, being capable of implementing more than one computation, unlike artificial neural-network units with fixed activation functions. We investigate this flexibility by modeling how synaptic activation patterns of real-world stimuli affect dendritic integration and the resultant neuronal computation. Our work bridges the gap between biophysical mechanisms and computation, linking neuronal input integration to pattern recognition.

neuroscience↗

bioRxiv2023

Mild blast TBI raises gamma connectivity, EEG power, and reduces GABA interneuron density

At least one traumatic brain injury (TBI) will be experienced by approximately 50-60 million of the worlds population in their lifetime and is the biggest cause of death and disability in those under 40. Mild traumatic brain injury (mTBI) can induce subtle changes but have long-lasting effects that may be difficult to detect through conventional neurological assessment, including standard clinical imaging techniques. These changes can lead to an increased risk of future neurodegeneration and emphasises the need to use more sensitive diagnostic tools such as EEG in order to identify injury and opportunities for therapeutic intervention. In this study, we investigated electrophysiological and histopathological changes in a rat model of mild blast-induced TBI. We used a 32-channel EEG electrode array to detect global and local changes in neural activity and functional connectivity in acute (3 to 4-hours) as well as chronic phases (1 and 3-months) post-injury. GABAergic inhibitory interneurons, crucial for maintaining an excitatory/inhibitory balance, were quantified using immunohistochemistry. Mild blast-induced TBI had minimal effects on resting power and connectivity at the acute timepoint but resulted in resting-state global power increases at all frequencies as well as a relative power increase in slow-wave frequencies in the chronic phase post-injury. Functional connectivity increases in the gamma frequency along with increases in power in the chronic phase pointed towards an alteration in the excitatory/inhibitory balance. Indeed, electrophysiological changes were associated with reduced density of GABAergic interneurons at 7-days, 1-month, and 3months post-injury, with a decrease in somatostatin-positive cell density in the 5th layer of all cortical regions of interest, and a parvalbumin decrease in the 5th layer of the primary auditory cortex. In contrast, the total number of neurons, measured by NeuN did not change significantly, thus demonstrating a biased impact on inhibitory interneuron populations. Our work demonstrates that the techniques and metrics of injury assessment employed in this study are sensitive enough to reflect the subtle changes present in mTBI and therefore hold potential clinical relevance. By using non-invasive EEG assessments and histopathology, we were able to reveal direct correlates and potential sources of the abnormalities caused by mild blast-induced TBI.

neuroscience↗

bioRxiv2023

Bidirectional Generative Adversarial Representation Learning for Natural Stimulus Synthesis

Thousands of species use vocal signals to communicate with one another. Vocalisations carry rich information, yet characterising and analysing these complex, high-dimensional signals is difficult and prone to human bias. Moreover, animal vocalisations are ethologically relevant stimuli whose representation by auditory neurons is an important subject of research in sensory neuroscience. A method that can efficiently generate naturalistic vocalisation waveforms would offer an unlimited supply of stimuli with which to probe neuronal computations. While unsupervised learning methods allow for the projection of vocalisations into low-dimensional latent spaces learned from the waveforms themselves, and generative modelling allows for the synthesis of novel vocalisations for use in downstream tasks, there is currently no method that would combine these tasks to produce naturalistic vocalisation waveforms for stimulus playback. In this paper, we demonstrate BiWaveGAN: a bidirectional Generative Adversarial Network (GAN) capable of learning a latent representation of ultrasonic vocalisations (USVs) from mice. We show that BiWaveGAN can be used to generate, and interpolate between, realistic vocalisation waveforms. We then use these synthesised stimuli along with natural USVs to probe the sensory input space of mouse auditory cortical neurons. We show that stimuli generated from our method evoke neuronal responses as effectively as real vocalisations, and produce receptive fields with the same predictive power. BiWaveGAN is not restricted to mouse USVs but can be used to synthesise naturalistic vocalisations of any animal species and interpolate between vocalisations of the same or different species, which could be useful for probing categorical boundaries in representations of ethologically relevant auditory signals.

neuroscience↗

bioRxiv2022

Bioinspired Stretchable Transducer for Wearable Continuous Monitoring of Respiratory Patterns in Humans and Animals

We report a bio-inspired continuous wearable respiration sensor modeled after the lateral line system of fish which is used by the fish for detecting mechanical disturbances in the water. Despite the clinical importance of monitoring respiratory activity in humans and animals, continuous measurements of breathing patterns and rates are rarely performed in or outside of clinics. This is largely due to conventional sensors being too inconvenient or expensive for wearable sensing for most individuals and animals. The bio-inspired air-silicone composite transducer is placed on the chest and measures respiratory activity by continuously measuring the force applied to an air channel embedded inside a silicone-based elastomeric material. The force applied on the surface of the transducer during breathing changes the air pressure inside the channel which is measured using a commercial pressure sensor and mixed-signal wireless electronics. We extensively characterized the transducer produced in this work and tested it with humans, dogs, and laboratory rats. The bio-inspired air-silicone composite transducer may enable the early detection of a range of disorders that result in altered patterns of respiration. The technology reported can also be combined with artificial intelligence and cloud computing to algorithmically detect illness in humans and animals remotely, reducing unnecessary visits to clinics.

bioengineering↗

bioRxiv2021

Composite receptive fields in the mouse auditory cortex

AO_SCPLOWBSTRACTC_SCPLOWA central question in sensory neuroscience is how neurons represent complex natural stimuli. This process involves multiple steps of feature extraction to obtain a condensed, categorical representation useful for classification and behavior. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features when probed with conspecific songs. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners, or a generic characteristic of central auditory systems in different animals is, however, unknown. To address this question, we have recorded responses from auditory cortical neurons in mice, and characterized their receptive fields using mouse ultrasonic vocalizations (USVs) as a natural and ethologically relevant stimulus and pitch-shifted starling songs as a natural but ethologically irrelevant control stimulus. We have found that auditory cortical neurons in the mouse display composite receptive fields with multiple excitatory and inhibitory subunits. Moreover, this was the case with either the conspecific or the heterospecific vocalizations. We then trained the sparse filtering algorithm on both classes of natural stimuli to obtain statistically optimal features, and compared the natural and artificial features using UMAP, a dimensionality-reduction algorithm previously used to analyze mouse USVs and birdsongs. We have found that the receptive-field features obtained with the mouse USVs and those obtained with the pitch-shifted starling songs clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. These results indicate that composite receptive fields are likely a generic property of central auditory systems in different classes of animals. They further suggest that the quadratic receptive-field features of the mouse auditory cortical neurons are natural-stimulus invariant.

neuroscience↗

bioRxiv2021

Fast adaptation of cooperative channels engendersHopf bifurcations in auditory hair cells

Since the pioneering work of Thomas Gold published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Termed the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ears mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive--especially at the high frequencies characteristic of mammalian hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has previously been proposed that a cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here, we ground our study on our previous model of hair-cell mechanotransduction, which relied on the cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, our model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. In contrast to the myosin-based mechanism, responsible for low-frequency relaxation oscillations in the vestibular hair cells of amphibians, the current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the single mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of mammalian hearing. SIGNIFICANCEHow the inner ear amplifies incident sounds at audible frequencies of several kilohertz is a key question that has remained unanswered despite decades of research into several candidate mechanisms. Here, we model the behavior of hair cells, the sensory receptors of the inner ear, and show that they can undergo oscillatory instabilities called Hopf bifurcations due to the effect of Ca2+ on the cooperative opening and closing of mechanotransduction ion channels. Close to the bifurcation point, a hair cell behaves as a nonlinear oscillator that can amplify its input on a cycle-by-cycle basis. We find that our proposed mechanism can operate in the kilohertz range.

biophysics↗