Konstantin V Anokhin

Kurchatov Institute · Neuroscience

Newly hatched domestic chicks are known to orient preferentially toward naturalistic stimuli, resembling a conspecific. Here, we examined to what extent this behavioral preference can be transcended by an artificial imprinting stimulus in both short-term and long-term tests. We also compared the expression maps of the plasticity-associated c-fos ge...

Post-traumatic stress disorder (PTSD) is defined by the International Classification as impairments to emotional state and reactions to a stressful situation in humans. the symptoms of PTSD include anxiety and intrusive memories of the traumatizing event, nightmares, irritability, increased awareness of danger or preoccupation with potential danger...

Functional differentiation of the hippocampus along its longitudinal septotemporal axis is beyond doubt, though the factors determining this subregional specificity remain controversial. The spatial specificity gradient of hippocampal place cells decreases along its longitudinal axis from the septal pole to the temporal area. This difference in the...

The development of post-traumatic stress disorder (PTSD) in humans includes a number of symptoms, the main being intrusive memories of the trauma, psychological and physiological hyperreactivity on reminding of the trauma, and increased anxiety, and specific memory impairments. Current models of PTSD in animals address the last three of these sympt...

The functional differentiation of the hippocampus along the longitudinal axis is firmly established, but the factors of this subregional specificity remain debatable. The spatial scale (the size of hippocampal place fields) has been shown to increase along the longitudinal axis from septal to temporal subregions. This difference in the scale of spa...

Most important events in the environment are complex in sensory terms. Integration of multimodal information relating to such complex signals by the brain is regarded by many investigators as a biological function of very early forms of consciousness. We report here use of a model of associative learning in mice in which electrocutaneous stimulatio...

Olfactory memory is one of the most ancient cognitive systems in the mammal brain and has its own neural structures and mechanisms. Most behavioral models of olfactory memory in laboratory animals use several training sessions, which significantly hinders the detection and study of the neural networks of the brain involved in the acquisition of thi...

It is generally assumed that if memory is disrupted by pharmacological inhibitors during its consolidation, it can be later acquired afresh. In our experiments, we trained day-old chicks in a one-trial passive avoidance task and interfered with memory formation using protein synthesis inhibitor anisomycin or NMDA receptor antagonist MK-801. Second...

Identification of the neural mechanisms of associative memory is one of the fundamental tasks in neuroscience. We report here use of a model of associative learning in mice in which formation of a memory of a neutral context and subsequent association of transient presentation of this context with an unconditioned electrocutaneous stimulus (footsho...

The neurophysiological mechanisms of the development of post-traumatic stress disorder (PTSD) in humans remain poorly understood and require experimental investigation in animal models. We report here studies of variation in the range of conditions for the acquisition of PTSD in a learned fear model in mice using electrocutaneous shocks (ECS) as th...

Current review is focused on the integrative functions of the retrosplenial cortex, which neurons are largely involved in spatial orientation and ambulation of an organism. We discuss anatomy and connectivity of the retrosplenial cortex in rats as well as the most recent findings concerning the behavioral specialization of its neurons observed usin...

We studied the effects of light and non-specific sound stimulation of domestic chick embryos on their filial preference as well as on the expression of two transcriptional factors c-Fos and Egr-1 and neurotrophin BDNF in the embryo brain. Prenatal light stimulation increased preference of the “natural” object, thus producing a priming effect. In th...

This review addresses the potentials of current methods of molecular ex vivo imaging of neurons involved in episodes of cognitive activity in experimental animals. We describe the principles on which the molecular identification of neurons activated in cognitive tasks are based, special attention being paid to the molecular marking of neuron activi...

Impairment of protein synthesis in the brain during learning prevents memory consolidation and results in amnesia, which until recently has been regarded irreversible. However, in some cases impaired memory could be restored by various “reminder” stimuli. The present study is based on the hypothesis that even in behaviorally profound amnesia, some...

This review addresses the potential of current methods of in vivo two-photon imaging of the activity of neurons involved in episodes of cognitive activity in animals. The principles of fluorescent two-photon microscopy are described and methods for in vivo imaging of neuron activity using calcium indicators of two types – calcium stains and genetic...

In this study, we describe use of Cre-mediated recombination to obtain a permanent genetic labeling of the brain neuronal networks activated during a new experience in animals. This method utilizes bitransgenic Fos-Cre-eGFP mice in which a green fluorescent protein is expressed upon tamoxifen-induced Cre-recombination only in the cells where immedi...

Understanding the neurophysiological mechanisms of human post-traumatic stress disorder (PTSD) requires development and employment of valid animal models. We explored a range of parameters for the induction of PTSD symptoms in mice using a model based on fear conditioning. Varying the footshock parameters we found that the level of conditioned fear...

Currently the model of associative memory in mammals most frequently used in neurobiological studies consists of acquisition of a conditioned reflex freezing reaction. As most studies address the mechanisms of learning in response to a sound stimulus, the question of the extent to which the patterns of forming associative memory are universal and a...

Reconnectable bundles consisting of thousands of optical fibers are shown to enable high-quality image transmission, offering a platform for the creation of implantable fiberscopes for minimally invasive in vivo brain imaging. Experiments on various lines of transgenic mice verify the performance of this fiberscope as a powerful tool for chronic in...

Many animal species are able to use context as a conditioned signal for learning. In some cases, the initial memorization of the context and its subsequent association with an unconditioned stimulus can be separated by a long period of time – a phenomenon termed the “context preexposure effect.” This type of associative learning is based on a remin...

Optical coupling between a single, individually addressable neuron and a properly designed optical fiber is demonstrated. Two-photon imaging is shown to enable a quantitative in situ analysis of such fiber-single-neuron coupling in the live brain of transgenic mice. Fiber-optic interrogation of single pyramidal neurons in mouse brain cortex is perf...

Cognitive tests on representative groups of freely behaving transgenic mice are shown to enable a quantitative characterization of reconnectable implantable fiber-optic neurointerfaces for optogenetic neurostimulation. A systematic analysis of such tests provides a robust quantitative measure for the cognitive effects induced by fiber-optic neurost...

This review is focused on the modern methods of in vivo two-photon imaging of activity of neurons involved in cognitive processes in experimental animals. We describe main principles of in vivo two- photon microscopy and optical imaging of neuronal activity with two types of calcium sensors: chemical dyes and genetically encoded calcium indicators....

Activity of NMDA receptors is a prerequisite for numerous but not all forms of neuronal plasticity and learning. The present study examined the role of NMDA receptors in standard, weak, and repeated passive avoidance training in young chicks. Injection of MK-801, an antagonist of NMDA receptor, prior to strong training episode impaired subsequent m...

We studied pro-cognitive effect of two heterocyclic low-molecular-weight compounds that serve as non-peptide analogues of soluble fragment of amyloid peptide precursor (sAPP). Intracerebroventricular and systemic administration of peptide mimetics P2 and P5 improved weak memory on the model of passive avoidance in chicks and in the object location...

We evaluated the effect of hippocampal injection of lentiviral particles p156-CMV-EGFP on behavior, learning, and microglial Iba1+ cells activation in mice. Testing in the open field and elevated plus-maze revealed higher anxiety levels in lentiviral-injected mice in comparison with animals injected with vehicle. At the same time, lentivirus inject...

Classical fear conditioning occurs when a conditioned stimulus (usually simple neutral stimulus, like a sound or light) is paired with an unconditioned stimulus (shock). Neuronal mechanisms underlying formation of the fear conditioning memory are investigated well, especially in amygdala, hippocampus and prelimbic cortex. Сoncurrently there is the...

Up to date, rodent fear conditioning is the most commonly used model of mammalian associative memory in neurobiology. Since the mechanisms of associative memory in this model are mainly studied using audi tory fear conditioning, the question about the generality of this mechanisms in respect to other conditioned stimuli remains open. The aim of thi...

Accumulation of c-Fos and Arc proteins in neurons in different regions of the hippocampus after single trial of contextual fear conditioning was studied by using immunohistochemical staining. We found that the dynamics of the c-Fos and Arc expression has a biphasic pattern: the fi rst peak was observed in 15-30 min after learning and the second les...

Accumulation of c-Fos and Arc proteins in neurons in different regions of the hippocampus after single trial of contextual fear conditioning was studied by using immunohistochemical staining. We found that the dynamics of the c-Fos and Arc expression has a biphasic pattern: the first peak was observed in 15-30 min after learning and the second less...

A bundle of individually addressable optical fibers is shown to enable three-dimensional optical readout from single neurons in live brain, as well as in intact brain extracted from transgenic mice. With individual fibers in the bundle being only a few microns in diameter, single neurons are readily resolved in brain images transmitted by the fiber...

The aim of the present work was to study the role of histone acetylation in brain cells in the formation of memory in neonatal chicks by investigating the effects of intracerebral administration of the histone deacetylase inhibitor trichostatin A on the formation of memory in “weak” learning by chicks of a passive avoidance task and on the expressi...

We report here studies in which a controlled history of sequential learning of two skills was created with the aim of identifying the pattern of activation of neurons for the first skill on formation of the second. Animals were initially trained to an operant drinking behavior requiring use of the whiskers on the left or right side (a “whisker-depe...

Methods of optical physics offer unique opportunities for the investigation of brain and higher nervous activity. The integration of cutting-edge laser technologies and advanced neurobiology opens a new cross-disciplinary area of natural sciences - neurophotonics-focusing on the development of a vast arsenal of tools for functional brain diagnostic...

The effects of an inhibitor of protein kinase Mζ on long-term memory were studied using the model of taste aversion in newborn chicks. Memory was impaired by intracerebral injection of 10 or 20 nmol of ζ-inhibiting peptide 24 h after training. Memory impairment was found 2 h after peptide administration, and repeated examination 24 h after treatmen...

In this work we aimed to create a controlled history of two sequential trainings in order to find out activation patterns of "the first task" neurons during the second task learning. Rats were first trained to perform instrumental water rewarded behavior that required using left or right whiskers (a conditioned "whisking" task), and then to perform...

The aim of the work was to examine the role of histone acetylation in memory consolidation in newborn chicks. We studied the effects of histone deacetylase inhibitor trichostatin A (TSA) on a "weak" memory for passive avoidance and on expression of two transcription factors c-Fos and ZENK known to play a role in neuronal plasticity in the chick bra...

Methods of optical physics offer unique opportunities for the investigation of brain and higher nervous activity. The integration of cutting-edge laser technologies and advanced neurobiology opens a new cross-disciplinary area of natural sciences neurophotonics focusing on the development of a vast arsenal of tools for functional brain diagnostics,...

The present study analyzed expression of transcriptional factors c-Fos and ZENK in 9-day-old pied flycatcher nestlings’ (Ficedula hypoleuca) telencephalic auditory centers (field L, caudomedial nidopallium and caudomedial mesopallium) involved in the acoustically guided defense behavior. Species-typical alarm call was presented to the young in thre...

We studied the formation of spatial and nonspatial memory in mice during learning in three different condensed versions of Morris water maze task. Learning in combined version caused the formation of both spatial and nonspatial memory, whereas learning in condensed versions (spatial and nonspatial) led to memory formation specific for the version.

The present study analyzed expression of transcriptional factors c-Fos and ZENK in 9-day-old pied flycatcher nestlings' (Ficedula hypoleuca) telencephalic auditory centers (field L, caudomedial nidopallium and caudomedial mesopallium) involved in the acoustically-guided defense behavior. Species-typical alarm call was presented to the young in thre...

Two-photon excitation is shown to substantially enhance the locality of fiber-based optical interrogation of strongly scattering biotissues. In our experiments, a high-numerical-aperture, large-core-are fiber probe is used to deliver the 200-fs output of a 100-MHz mode-locked ytterbium fiber laser to samples of live mouse brain, induce two-photon f...

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfac...

Coherent cancellation of third-harmonic generation (THG) in a tightly focused laser beam is shown to enable a label-free imaging of individual neurons in representative brain tissues. The intrinsic coherence of third-harmonic buildup and cancellation combined with the nonlinear nature of the process enhances the locality of the dark signal in THG,...

Memory consolidation is a term used to describe the process of memory stabilization from labile, easily disrupted state into disruption-resistant long-term form. Protein synthesis inhibitors injected before or immediately after learning episode, produce significant amnesia. However in a limited number of studies the possibility of memory recovery a...

Modern optical methods (multiphoton and light-sheet fluorescent microscopy) allow 3D imaging of large specimens of the brain with cell resolution. It is therefore essential to refer the resultant 3D pictures of expression of transgene, protein, and other markers in the brain to the corresponding structures in the atlas. This implies counterstaining...

The method of contrasting with iodine ions was developed to obtain high-resolution 3D images of large biological specimens using a synchrotron X-ray microtomography unit. It was shown that the samples (late mouse embryos) treated with 50% Lugol solution with addition of 25% ethanol for 48 h followed by a 48-h washout in phosphate buffered saline ha...

We analyzed the expression of transcription factor c-Fos induced by neural activity in the mouse brain after acoustic stimulation. The brain sections of the animals subjected to acoustic stimulation and controls were immunohistochemically stained for c-Fos protein. Statistical parametric mapping (SPM) was used to identify group differences in th...

In this work, the investigation of network activity of mirror neurons systems in animal brains depending on experience (existence or absence performance of the shown actions) was carried out. It carried out the research of mirror neurons network in the C57/BL6 line mice in the supervision task of swimming mice-demonstrators in Morris water maze. It...

doi 10.1007/s11055-013-9731-2 Hippocampal activity in C57BL/6 mice was studied during exploration of novel spaces of different levels of complexity and learning by neuromapping using the induction of c-Fos protein by nervous activity. c-Fos-immunopositive neurons were counted at eight levels along the whole of the rostrocaudal axis of the hippocamp...

Tricyclics and Selective Serotonin Reuptake Inhibitors (SSRIs) are probably the most widely employed reference antidepressants in animal studies on depression. Using imipramine and citalopram, we sought to assess which drug would be more appropriate as pharmacological reference in paradigms of depression in C57BL6N mice by measuring their effect on...

We analyzed the expression of transcription factor c-Fos induced by neural activity in the mouse brain after acoustic stimulation. The brain sections of the animals subjected to acoustic stimulation and controls were immunohistochemically stained for c-Fos protein. Statistical parametric mapping (SPM) was used to identify group differences in the a...

A fiber-bundle microprobe coupled to a confocal optical microscope is shown to enable multicolor in vivo fluorescence brain imaging. A bundle of several thousands of 2.4-mu m-diameter optical fibers is employed to deliver multiwavelength laser excitation radiation and to transmit multicolor images from hippocampus tissues in living transgenic mice...

Antiresonance-guiding hollow-core fibers are shown to enable highly sensitive detection of cell proliferation probes using Raman scattering within the region where the cellular Raman activity is minimal. We demonstrate that such fibers can substantially reduce the level of the background compared to standard index-guiding optical fibers, thus radic...

We developed a method to detect and superimpose neuronal populations involved in two different episodes of activity in the brain of single animal. This method is based on usage of two transcriptional factors with different accumulation curves, c-Fos and pCREB, as the markers. The overlap of neuronal populations involved in performance of spatial an...

Optical fibers are employed to sense fingerprint molecular vibrations in ex vivo experiments on the whole brain and detect cell proliferation probes in a model study on a quantitatively controlled solution. A specifically adapted spectral filtering procedure is shown to allow the Raman signal from molecular vibrations of interest to be discriminate...

We studied the effects of training on DNA synthesis intensity in mouse brain. Brain cells where DNA synthesis-associated processes took place under the influence of training were detected by immunohistochemical labeling of DNA molecules with synthetic thymine analogue 5-bromo-2'-deoxyuridine. The number of 5-bromo-2'-deoxyuridine-positive cell incr...

We compared the effects of electrical stimulation of primary dissociated neuronal cultures cultured on microelectrode arrays in terms on the expression of c-fos transcriptional factor that is involved in plastic reorganization in neurons. Dissociated hippocampal neurons cultured on multielectrode arrays were exposed to two stimulation protocols: hi...

Effects of glutamate receptor modulator dimebon on memory consolidation and reconsolidation were investigated in passive avoidance paradigm in newborn chicks. Systemic administration of 0.1 mg/kg dimebon 5 min before or 4 h after "weak" training resulted in formation of long-term memory. Dimebon administration in combination with memory reactivatio...

The effects of serotonin and glutamate on c-fos expression and c-Fos colocalization with DNA were immunohistochemically studied in defense behavior command neurons R-LPa2-3 in snail Helix lucorum. Simultaneous neurotransmitter application resulted in increased c-Fos-immunoreactivity and colocalization with DNA-specific stain Hoechst 33342 in LPa2 a...

Possible mechanisms of recovery of the memory impaired during consolidation process were investigated. In mice, amnesia was induced by intraperitoneal cycloheximide (100 mg/kg) administration 20 min before exposure to tone signal combined with footshock (2 sec, 0.5 mA). Reminder by the footshock (2 sec, 0.5 mA) 24 h after the learning procedure res...

We studied the effects of histone deacetylase inhibitor that stimulates transcriptional activity via histone hyperacetylation on memory formation. Sodium butyrate and sodium valproate enhanced memory in chicks following "weak" training with memory transfer into long-term state. Quantitative analysis of c-Fos and ZENK transcriptional factor gene exp...

We studied the involvement of DNA synthesis into molecular mechanisms of long-term memory. Nucleoside analogue 5-bromo-2'-deoxyuridine (BrdU) is known to incorporate into synthesizing DNA and prevent subsequent DNA replication from this region. To investigate the effect of BrdU administration on long-term memory, terrestrial gastropods edible snail...

The plasticity of neural networks is a complex process determined by changes in physiological status, gene expression and phenotype of a cell. A detailed study of this process dynamics requires the simultaneous recording of electrical and genomic activities in networks of neurons. This sets up one of the tasks for modern neuroscience as development...

Small-core photonic-crystal fibers (PCFs) are shown to enhance the locality of optical interrogation in fiber-probe-based imaging. We demonstrate that, in a typical fluorescence imaging experiment, the longitudinal dimension of the interrogated region closely follows the amtan−1θd scaling with the effective mode radius am and the beam-divergence an...

Open field behavior is well known to depend on physical characteristics of the apparatus. However many of such effects are poorly described especially with using of modern methods of behavioral registration and analysis. The previous results of experiments on the effect of arena size on behavior are not numerous and contradictory. We compared the b...

Large-core hollow photonic-crystal fibers (PCFs) are shown to enable a fiber-format air-guided delivery of ultrashort infrared laser pulses for neurosurgery and nonlinear-optical imaging. With an appropriate dispersion precompensation, an anomalously dispersive 15-μm-core hollow PCF compresses 510-fs, 1070-nm light pulses to a pulse width of about...

Levels of the c-Fos protein expression in neurons were used as an index of neural activation in the hippocampus of C57BL/6 mice after their exploration of novel environments. C-Fos expression was measured at 8 levels along the rostrocaudal axis of the hippocampus. In Experiment 1, C57BL/6 mice were trained in a modified 8-arm radial maze to find th...

An extended-cavity Cr:forsterite laser is integrated with a photonic-crystal fiber soliton frequency shifter and a periodically poled lithium niobate spectrum compressor for simultaneous harmonic-generation and coherent Raman brain imaging. Adapting the laser beam focusing geometry to the tissue morphology is shown to enable complementarity enhance...

Suitably designed optical fibers are shown to offer a powerful tool for functional brain mapping, facilitating the detection of Cherenkov radiation generated by relativistic positrons from positron-emitting radionuclides. Fiber probes support a low-loss delivery of the high-intensity short-wavelength part of the Cherenkov spectrum, which is strongl...

Immunohistochemical detection of c-Fos protein on serial frontal sections of pied flycatcher nestling brains was used to map visual structures involved in the sensory support of the early forms of feeding behavior. Quantitative analysis of c-Fos protein content was performed in the higher representations of the thalamofugal (Wulst) and tectofugal (...

A supercontinuum source based on a highly nonlinear photonic-crystal fiber (PCF) is combined with a hollow-core photonic-band-gap fiber (PBGF) spectral filter for a multiplex, high-repetition-rate fiber-based interrogation of fluorescent-protein neuron-activity reporters, and fluorophore conjugate antibody labels in the brain of transgenic mice. Th...

A representative confocal image of fluorescent antibody staining revealing IEG expression in HVC after undirected singing. HVC neurons expressed ZENK (green nuclear stain), c-Fos (red nuclear stain) or both genes simultaneously (yellow). Transverse section. Scale bar, 70 µm. (TIF)

Specialized neural pathways, the song system, are required for acquiring, producing, and perceiving learned avian vocalizations. Birds that do not learn to produce their vocalizations lack telencephalic song system components. It is not known whether the song system forebrain regions are exclusively evolved for song or whether they also process inf...