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Dr. Oxana Eschenko

Address: Spemannstr. 38
72076 Tübingen
Room number: 230
Phone: +49 7071 601 1679
Fax: +49 7071 601 652
E-Mail: oxana.eschenko

 

Picture of Eschenko, Oxana, Dr.

Oxana Eschenko

Position: Postdoctoral Fellow  Unit: Logothetis

The scientific interest of my research group is to better understand the neurophysiological mechanisms of noradrenergic (NA) neuromodulation in the brain. The NA system mediates many cognitive processes such as attention, perception, learning and memory. Dysfunction in noradrenergic system often leads to various psychiatric disorders.

The core of the NA system is a small brainstem nucleus Locus Coeruleus (LC). The LC-NA neurons project extensively throughout the brain, innervating the spinal cord, the brain stem, hypothalamus, cerebellum, thalamic relay nuclei, amygdala, basal telencephalon, as well as the cortex. As opposed to direct synaptic neurotransmission (wired transmission), the axons of NA neurons commonly have characteristic varicosities by means of which NA is secreted and diffused through large volumes of tissue (volume transmission), thereby affecting simultaneously multiple and diverse population of neurons. The mechanisms underlying the specificity of neuromodulatory effects at different projection targets are poorly understood. A major advance in understanding the neurophysiological mechanisms of NA neuromodulation in the brain may be achieved by monitoring neuromodulatory effects at multiple brain regions simultaneously and at different scales.

The specific aims are the following: 1) to describe the effective (functional) connectivity of the LC in the rat brain; 2) to characterize temporal interactions between LC activity and its cortical and subcortical targets during spontaneous and sensory-evoked activity in anesthetized and behaving rats; and 3) to study how the modulation of LC activity affects cortical state, sensory responses, and sensory-guided behavior.     

Project 1. Mapping of the functional connectivity of the LC in the rat brain.

We compared the labeling produced by a classical anatomical tracer (fluorescent dextran) and by MRI-visible tracer (Mn2+) injected simultaneously in LC. The major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor (M1) and somatosensory (S1) cortices, hippocampus and amygdala were detected using manganese-enhanced MRI (MEMRI). MEMRI method consistently failed to reliably label several minor but also major targets of LC, notably the thalamus (Eschenko et al., 2011). The lack of Mn2+ labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. These results will be complemented by mapping of the functional connectivity of the LC projections using combined microstimulation and fMRI.  

This project is collaboration with Dr. H.C. Evrard and R. Neves.

Eschenko O, Evrard HC, Neves RM, Beyerlein M, Murayama Y, Logothetis NK. (2011) Tracing of noradrenergic projections using manganese-enhanced MRI, NeuroImage, in print.

Project 2. Differential noradrenergic modulation in the rat somatosensory and prefrontal cortex.

We compared the effects of systemic (i.p.) or local (into LC) application of clonidine, an alpha2-receptor agonist, which is known to inhibit LC-NA neurons, on sensory responses in S1 and PFC, the two cortical targets of LC. Local application of clonidine resulted in complete cessation of both spontaneous and evoked activity of LC neurons to mild foot shocks (FS). Absence of LC signaling did not affect S1 responses, while both increased and decreased responses were observed in PFC (Fig.1). Systemic clonidine produced a transient decrease of LC spontaneous activity, while LC evoked responses were preserved. This manipulation decreased signal-to-noise ratio (SNR) in S1 neurons, while sensory signaling in PFC was, overall,  increased. We now extend this project to recordings in VTA.

This project is collaboration with Dr. S. Sara and a part of the PhD study of S. van Keulen. 

Project 3. Noradrenergic modulation of the cortical state and state-dependent sensory coding.

The neural responses to sensory stimulation are more robust when cortical activity is decorrelated (or desynchronized state). Moreover, the sensory responses markedly differ when stimulus occurred in the depolarized (Down) or hyperpolarized (Up) state. Inhibition of LC activity (e.g. by clonidine) leads to more synchronized activity in cortex. The electrical microstimulation of LC (e.g. trains of pulses at 50Hz for 500ms) applied during synchronized state produces a transient (~1-2s) desynchronization. The sensory responses resembled such during Up state if LC stimulation preceded the sensory stimulus.

This project is collaboration with Dr. S. Panzeri and Dr. C. Magri and a part of master thesis of R. Neves.

Project 4. Investigation of the effects of electrical microstimulation of the Locus Coeruleus in anesthetized and behaving rats.

We performed recording/stimulation unsing the same electrode tip placed in the LC. Electrical stimulation produced a sustained inhibition(40-120ms) of LC neurons at the stimulation site. There was no effect of pulse duration (range: 0.1-0.5ms) or current intensity (range: 0.01-0.2mA) on LC inhibition at the stimulation site. The linear relations between both factors and the duration of LC inhibitions were onserved at longer distances from the stimulation site. Neural responses in the contralateral LC showed overall a shorter inhibition (65±6ms). Trains of pulses (>200ms at 20-50Hz) delivered to the LC resulted in a transient desynchronization in mPFC.

This project is collaboration with Dr. A. Marzo.

Our results demonstrate that:

1) functional connectivity of LC with its projection targets could not be predicted from anatomical connectivity and may be context- or state dependent;

2) blocking the LC sensory-evoked discharge differentially affected signal processing in S1 and PFC as the opposite effects (decrease and increase in SNR) were observed with overall stronger modulation in PFC;

3) LC-NA system is involved in regulation of cortical state and therefore affect state-dependent sensory processing. 

4) Application of the electrical current to LC, as low as 0.01mA, may mimic a characteristic response of the LC-NE neurons to salient stimuli (a brief excitation followed by a prolonged inhibition), however only a relatively strong LC stimulation (trains of pulses) affect neural activity in the distal cortical targets of LC, e.g. mPFC.

Research Scientist

2006 – present Max Planck Institute for Biological Cybernetics; Dept. Physiology of Cognitive Processes.

Education

1999 PhD in Neurophysiology, Moscow State University, Moscow, Russia

1993 

Master Diploma in Neurophysiology, Moscow State University, Moscow, Russia

Research Experience

2003-2006 Postdoctoral researcher at Dept. of Neuromodulation, Neuroplasticity & Cognition CNRS, UMR 7102; University Pierre & Marie Curie, Paris, France

2000-2003 Research assistant at Dept. of Psychology, University of Washington, Seattle, USA

1999-2000 Research fellow at Dept. of Pharmacology and Clinical Pharmacology, University of Turku, Finland

 

Eschenko O (July-6-2014) Invited Lecture: The role of Locus Coeruleus for sensory processing within the mesocortical dopaminergic pathway, 9th FENS Forum of Neuroscience, Milano, Italy9 ( R10101) .
Salient events evoke burst-like responses of noradrenergic (NE) neurons of the Locus Coeruleus (LC) and dopaminergic (DA) neurons of the ventral tegmental area (VTA). The associated NE and DA release modulates signal processing in the projection targets of LC and VTA, which is beneficial for selection of adaptive behavioral response. In the rat, terminal fields of both LC-NE and VTA-DA neurons converge in the medial prefrontal cortex (mPFC), a cortical area controlling many cognitive capacities. We investigated the role of LC phasic activation for sensory representations in two LC targets by simultaneous electrophysiological recording in LC, VTA and mPFC and pharmacological manipulation of LC activity. Under urhetaine anestesia, noxious stimulation (foot shock, FS) produces a robust short-latency (~20 ms) excitation/inhibition response of LC-NE neurons. Populations of VTA and mPFC neurons also exhibit phasic excitatory and inhibitory responses, yet with longer latencies (~100 ms). Supression of LC spontaneous and evoked activity by iontophoretic injection of clonidine, an alpha2-adrenergic receptor agonist, disinibited a substantial proportion of VTA-DA and mPFC pyramidal neurons regardless of their FS-responsiveness. Furthermore, LC inhibition bidirectionally modulated the VTA-DA and mPFC resposes to noxious stimulation. The ongoing and evoked activity of VTA non-DA neurons was unaffected. These results suggest that depending on the motivational valence of a salient event, the LC-NE system may selectively enhance or supress signalling within different and, possibly, competing mesolimbic and mesocortical pathways. This hypothesis is being currently tested in behaving animals engaiged in a sensory cue-guided reward-motivated operant task.
html CiteID: Eschenko2014

Logothetis NK , Besserve M , Eschenko O , Murayama Y , Augath M , Steudel T , Evrard HC and Oeltermann A (July-2013) Keynote Lecture: Studying large-scale brain networks: electrical stimulation and neural-event-triggered fMRI, Twenty-Second Annual Computational Neuroscience Meeting (CNS*2013), Paris, France, BMC Neuroscience14 (Supplement 1) A1.
The brain is "the" example of an adaptive, complex system. It is characterized by ultra-high structural complexity and massive connectivity, both of which change and evolve in response to experience. Information related to sensors and effectors is processed in both a parallel and a hierarchical fashion. The connectivity between different hierarchical levels is bidirectional, and its effectiveness is continuously controlled by specific associational and neuromodulatory centers. In the study of such systems one major problem is the adequate definition for an elementary operational unit (often called an "agent"), because any such module can be a complex system in its own right and may be recursively decomposed into other sets of units. A second difficulty arises from the synergistic organization of complex systems and of the brain in particular. Synergy here refers to the fact that the behavior of an integral, aggregate, whole system cannot be trivially reduced to, or predicted from, the components themselves. Localizing and comprehending the neural mechanisms underlying our cognitive capacities demands the combination of multimodal methodologies, i.e. it demands concurrent study of components and networks; one way of doing this, is to combine invasive methods which afford us direct access to the brain's electrical activity at the microcircuit level with global imaging technologies such as magnetic resonance imaging (MRI). In my talk, I'll discuss two such methodologies: Direct Electrical Stimulation and fMRI (DES-fMRI) and Neural-Event-Triggered fMRI (NET-fMRI). DES-fMRI can be used in hopes of gaining insight into the functional or effective connectivity underlying DES-induced behaviors. Yet, our first findings suggest that DES has an important limitation: It clearly demarcates all monosynaptic targets of a stimulated site, but it largely fails to reveal polysynaptic cortico-cortical connectivity. NET-fMRI, on the other hand, appears to offer great potential for mapping whole-brain activity that is associated with individual local events. In the second part of my talk, I'll describe the characteristic states of widespread cortical and subcortical networks that are associated with the occurrence of hippocampal sharp waves and ripples; the brief aperiodic episodes associated with memory consolidation.
html doi CiteID: LogothetisEMASEBO2013

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Articles (23):

Marzo A Person, Totah NK Person, Neves RM Person, Logothetis NK Person and Eschenko O Person (June-2014) Unilateral electrical stimulation of rat locus coeruleus elicits bilateral response of norepinephrine neurons and sustained activation of medial prefrontal cortex Journal of Neurophysiology 111(12) 2570-2588.
Logothetis NK Person, Eschenko O Person, Murayama Y Person, Augath M Person, Steudel T Person, Evrard HC Person, Besserve M Person and Oeltermann A Person (November-2012) Hippocampal-cortical interaction during periods of subcortical silence Nature 491(7425) 547–553.
Mamedov I Person, Engelmann J Person, Eschenko O Person, Beyerlein M Person and Logothetis NK Person (February-2012) Dual-functional probes towards in vivo studies of brain connectivity and plasticity Chemical Communications 48(22) 2755-2757.
Eschenko O Person, Magri C Person, Panzeri S Person and Sara SJ (February-2012) Noradrenergic Neurons of the Locus Coeruleus Are Phase Locked to Cortical Up-Down States during Sleep Cerebral Cortex 22(2) 426-435.
Eschenko O Person, Evrard HC Person, Neves RM Person, Beyerlein M Person, Murayama Y Person and Logothetis NK Person (February-2012) Tracing of noradrenergic projections using manganese-enhanced MRI NeuroImage 59(4) 3252–3265.
Eschenko O Person, Canals S Person, Simanova I and Logothetis NK Person (October-2010) Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI Magnetic Resonance Imaging 28(8) 1165-1174.
Eschenko O Person, Canals S Person, Simanova I , Beyerlein M Person, Murayama Y Person and Logothetis NK Person (February-2010) Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies Neuroimage 49(3) 2544-2555.
Ramadan W , Eschenko O Person and Sara SJ (August-2009) Hippocampal sharp wave/ripples during sleep for consolidation of associative memory PLoS One 4(8) 1-9.
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Eschenko O Person and Sara SJ (November-2008) Learning-dependent, transient increase of activity in noradrenergic neurons of locus coeruleus during slow wave sleep in the rat: brain stem-cortex interplay for memory consolidation? Cerebral Cortex 18(11) 2596-2603.
Eschenko O Person, Ramadan W , Mölle M , Born J and Sara SJ (April-2008) Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning Learning and Memory 15(4) 222-228.
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Eschenko O Person and Mizumori SJY (May-2007) Memory influences on hippocampal and striatal neural codes: Effects of a shift between task rules Neurobiology of Learning and Memory 87(4) 495-509.
Eschenko O Person, Mölle M , Born J and Sara SJ (December-2006) Elevated sleep spindle density after learning or after retrieval in rats Journal of Neuroscience 26(50) 12914-12920.
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Mölle M , Yeshenko O Person, Marshall L , Sara S and Born J (July-2006) Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep Journal of Neurophysiology 96(1) 62-70.
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Mizumori SJ , Canfield JG and Yeshenko O Person (2005) Parallel and interrelated neural systems underlying adaptive navigation Integrative and Comparative Biology 45(3) 547-554.
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Yeshenko O Person, Guazzelli A and Mizumori SJ (2004) Context-dependent reorganization of spatial and movement representations by simultaneously recorded hippocampal and striatal neurons during performance of allocentric and egocentric tasks Behav Neurosci 118(4) 751.
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Mizumori SJ , Yeshenko O , Gill KM and Davis DM Person (2004) Parallel processing across neural systems: implications for a multiple memory system hypothesis Neurobiol Learn Mem 82(3) 278.
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Vekovischeva O , Aitta-Aho T , Echenko O Person, Kankaanpaa A , Seppala T , Honkanen A , Sprengel R and Korpi ER (2004) Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient mice Genes Brain Behav 3(5) 253.
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Nikolskaya K and Echenko O Person (2002) Alcohol addiction as the result of cognitive activity in altered natural magnetic field Electromagnetic Biology and Medicine 21(1) 1-18.
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Heikkila AT , Echenko O Person, Uusi-Oukari M , Sinkkonen ST and Korpi ER (2001) Morphine withdrawal increases expression of GABA(A) receptor epsilon subunit mRNA in locus coeruleus neurons Neuroreport 12(13) 2981.
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Vekovischeva O , Zamanillo D , Echenko O Person, Seppala T , Uusi-Oukari M , Honkanen A , Seeburg PH , Sprengel R and Korpi ER (2001) Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits J Neurosci 21(12) 4451.
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Nikolskaia K , Eshchenko OV Person and Shpinkova VN (2000) Magnetic field and alcohol addiction Biofizika 45(5) 941.
Nikolskaya KA , Yeshchenko OV Person and Pratusevich V (1999) The opioid system and magnetic field perception Electro- and Magnetobiology 18(3) 277-290.
Eshchenko OV Person, Nikolskaia KA , Deigin VI and Iarova EP (1998) Psychostimulant effect of the synthetic analog of dermorphin Biull Eksp Biol Med 126(9) 252.

Posters (29):

Totah N Person, Neves RM Person, Katakalidis G Person, Logothetis NK Person and Eschenko O Person (July-8-2014): Effects of Long-Term Administration of Atomoxetine on Attentional Set-Shifting and Activity in the Rat Locus Coeruleus and Prefrontal Cortex, 9th FENS Forum of Neuroscience, Milano, Italy.
Van Keulen S Person, Logothetis NK Person and Eschenko O Person (July-6-2014): Alerting Effect of the Direct Electrical Stimulation of the Locus Coeruleus on the Acoustic Startle Response in the Rat, 9th FENS Forum of Neuroscience, Milano, Italy.
Safaai H , Neves R Person, Eschenko O Person, Logothetis NK Person and Panzeri S Person (July-2014): A dynamical systems model of the effect of Locus Coeruleus firing on single trial cortical state dynamics, Twenty-Third Annual Computational Neuroscience Meeting (CNS*2014), Québec City, Canada, BMC Neuroscience, 15(Suppl 1) P73.
Totah N Person, Neves R Person, Panzeri S Person, Logothetis NK Person and Eschenko O Person (June-2014): Characterization of the Effects of Tonic and Phasic Norepidrine Release on Layer-Specific Prefrontal Cortex and Primary Somatosensory Cortex Activity, AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles, Santorini, Greece.
Eschenko O Person, Novitskaya Y Person, Sara S and Logothetis NK Person (June-2014): Ripple-Triggered Stimulation of the Locus Coeruleus during Post-Learning Sleep Impairs Memory Consolidation, AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles, Santorini, Greece.
Eschenko O Person, Besserve M Person, Murayama Y Person, Evrard H Person, Beyerlein M Person, Oeltermann A Person and Logothetis NK Person (November-13-2013): BOLD responses associated with hippocampal ripples in the rat brain, 43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013), San Diego, CA, USA.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (September-2013): Suppression of noradrenergic and dopaminergic neurotransmission differentially affects detection of behaviorally relevant auditory stimuli, MCC 2013: Neural Circuits for Adaptive Control of Behavior, Paris, France.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (September-2013): Suppression of noradrenergic and dopaminergic neurotransmission differentially affects detection of behaviorally relevant auditory stimuli, 45th Meeting of the European Brain and Behavior Society (EBBS 2013), München, Germany.
Eschenko O Person, Beyerlein M Person, Oeltermann A Person and Logothetis NK Person (October-2012): BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia, 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012), New Orleans, LA, USA.
Neves RM Person, van Keulen S Person, Logothetis NK Person and Eschenko O Person (October-2012): Locus coeruleus noradrenergic system mediates the transient cortical activation evoked by nociceptive stimulation, 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012), New Orleans, LA, USA.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (July-2012): Differential Noradrenergic Modulation Of Sensory Processing In The Rat Somatosensory And Prefrontal Cortex, 8th Forum of European Neuroscience (FENS 2012), Barcelona, Spain.
Novitskaya Y Person, Logothetis NK Person and Eschenko O Person (July-2012): Noradrenergic Modulation Of Cortical And Hippocampal Activity During Natural Sleep In Rats, 8th Forum of European Neuroscience (FENS 2012), Barcelona, Spain.
Mamedov I Person, Engelmann J Person, Hagberg G Person, Eschenko O Person and Logothetis NK Person (May-8-2012): Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo by means of MRI, 20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012), Melbourne, Australia.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (October-2011): Differential noradrenergic modulation of the rat somatosensory and prefrontal cortex, 12th Conference of Junior Neuroscientists of Tübingen (NeNA 2011), Heiligkreuztal, Germany.
Lange Canhos L Person, Marzo A Person, Logothetis NK Person and Eschenko O Person (October-2011): The role of noradrenergic modulation for auditory discrimination learning in rats: development of a behavioral paradigm, 12th Conference of Junior Neuroscientists of Tübingen (NeNA 2011), Heiligkreuztal, Germany.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (September-2011): Differential noradrenergic modulation in the rat somatosensory and prefrontal cortex, Networks! 2011: 2nd German Neurophysiology PhD Meeting, Tübingen, Germany.
van Keulen S Person, Logothetis NK Person and Eschenko O Person (September-2011): Differential noradrenergic modulation in the rat somatosensory and prefrontal cortex, 43rd Meeting of the European Brain and Behavior Society (EBBS 2011), Sevilla, Spain.
Neves RM Person, Eschenko O Person, Evrard H Person, Beyerlein M Person and Logothetis NK Person (July-2010): Mapping noradrenergic projections from locus coeruleus using classical fluorescent tracer and MRI-visible contrast agent, 7th Forum of European Neuroscience (FENS 2010), Amsterdam, Netherlands.
Magri C Person, Eschenko O Person, Panzeri S Person and Sara SJ (July-2010): Noradrenergic neurons of the locus coeruleus are phase-locked to cortical updown states during sleep, 26th International Summer School of Brain Research: Slow Brain Oscillations of Sleep, Resting State and Vigilance, Amsterdam, Netherlands.
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Pietrajtis K Person, Sara SJ , Logothetis NK Person and Eschenko O Person (July-2010): Spike timing among neurons recorded simultaneously in locus coeruleus, ventral tegmental area and frontal cortex during somatosensory stimulation: LC leads!, 7th Forum of European Neuroscience (FENS 2010), Amsterdam, Netherlands.
Eschenko O Person, Pietrajtis K Person, Sara SJ and Logothetis NK Person (June-2010): Noradrenergic Modulation of Spontaneous Activity and Sensoryevoked Responses in Prefrontal Cortex, AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles, Santorini, Greece.
Neves RM Person, Eschenko O Person, Evrard H Person, Beyerlein M Person and Logothetis NK Person (November-2009): Anterograde analysis of noradrenergic projections in the rat forebrain using classical and manganese-enhanced MRI (MEMRI) tract-tracing, 10th Conference of Junior Neuroscientists of Tübingen (NeNa 2009), Ellwangen, Germany.
Pietrajtis K Person, Sara SJ , Logothetis NK Person and Eschenko O Person (November-2009): Dopaminergic and noradrenergic modulation of the rat prefrontal cortex: in vivo electrophysiological study, 10th Conference of Junior Neuroscientists of Tübingen (NeNa 2009), Ellwangen, Germany.
Simanova I , Canals S Person, Eschenko O Person and Logothetis NK Person (July-2008): Imaging of learning-associated brain activity in freely behaving rats using manganese-enhanced MRI (MEMRI), 6th Forum of European Neuroscience (FENS 2008), Geneva, Switzerland.
Yeshenko O Person, Moelle M , Marshall L , Born J and Sara SJ (2006): Locus coeruleus firing during SWS is time locked to slow oscillations: possible contribution of the noradrenergic system to off-line information processing in rats, Journal of Sleep Research, 15(Sulp) 11.
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Yeshchenko O Person and Nikolskaya K (July-1998): Forming of motivation is dependent on parameters of external magnetic field, 1998 Forum of European Neuroscience, Berlin, Germany, European Journal of Neuroscience, 10(Supplement) 418.
Nikolskaya K and Yeshchenko O Person (1998): A new behavioral model to study animal cognition, International Journal of Psychophysiology, 30(1-2) 122.
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Last updated: Tuesday, 23.09.2014