Anna Kiryk | Nencki Institute of Experimental Biology (original) (raw)

Papers by Anna Kiryk

Research paper thumbnail of Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 4, 2013

Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive l... more Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.

Research paper thumbnail of Kiryk Current Alzheimer Research 2011

In the present study, we used a new training paradigm in the intelliCage automatic behavioral ass... more In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12-and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

Research paper thumbnail of Genetic models to study adult neurogenesis

Acta biochimica Polonica, 2005

In the central nervous system (CNS) generation of new neurons continues throughout adulthood, whe... more In the central nervous system (CNS) generation of new neurons continues throughout adulthood, when it is limited to the olfactory bulb and hippocampus. The knowledge regarding the function of newly-generated neurons remains limited and is vigorously investigated using diverse approaches. Among these are genetically modified mice, most of them of knock-out type (KO). Results from 23 diverse KO mouse models demonstrate the importance of particular proteins (growth factors, nitric oxide synthases, receptors, cyclins/cyclin-associated proteins, transcription factors, etc.) in adult neurogenesis (ANGE) as well as separate it from developmental neurogenesis. These results bring us closer to revealing the function of newly generated neurons in adult brains.

Research paper thumbnail of Impaired rRNA synthesis triggers homeostatic responses in hippocampal neurons

Frontiers in Cellular Neuroscience, 2013

Research paper thumbnail of Impairment of adult brain neurogenesis does not promote depressive-like behavior

Frontiers in Behavioral Neuroscience, 1970

ABSTRACT Adult neurogenesis (ANGE) is the process of generation of new neurons in the brain of ad... more ABSTRACT Adult neurogenesis (ANGE) is the process of generation of new neurons in the brain of adult animals. Neuronal stem/precursor cells located in the subgranular zone of dentate gyrus (DG) and subventricular zone of the lateral ventricles proliferate and differentiate into mature neurons of the DG and olfactory bulb, respectively. Functional role of ANGE remains elusive, although it has been suggested to play an important role in the etiology of depression and its treatment with antidepressants. In our study we employed cyclin D2 gene knock-out (KO) mice showing approximately 10 times lower level of adult neurogenesis when compared to WT animals (Kowalczyk et al., J. Cell Biol., 2004). We have further characterized this deficit by demonstrating that KO mice show twice less astrocytes (GFAP-positive) when compared to WTs in the area of granular cell layer and hilus of the DG in the hippocampus formation. Furthermore, KO mice displayed a reduction of the apoptotic cells number (expressing active caspase-3) in analogous brain regions. Next, we have investigated whether the suppression of ANGE promotes the depressive-like behavior in KO mice when compared to WTs. We examined the initial depression level using a set of behavioral tests: tail suspension (TST), forced swimming (FST), nest building, novelty suppressed feeding, and anhedonic behavior test (using IntelliCage automated system). There was no significant effect of ANGE repression on KO mice behavior. We have also investigated whether the impairment of the adult brain neurogenesis alters the behavioral response of KO mice to antidepressants. Single injection of fluoxetine or imipramine (15 mg/kg) produced no difference in immobility between KO and WT animals in TST and FST. These result may suggest that ANGE suppression is rather a consequence than a cause of depressive behavior previously showed in animal models and human.

Research paper thumbnail of New hippocampal neurons are not obligatory for memory formation; cyclin D2 knockout mice with no adult brain neurogenesis show learning

Learning & Memory, 2009

The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to b... more The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs known for their side effects and the results obtained vary greatly. We used a novel approach, cyclin D2 knockout mice (D2 KO mice), specifically lacking adult brain neurogenesis to verify its importance in learning and memory. D2 KO mice and their wild-type siblings were tested in several behavioral paradigms, including those in which the role of adult neurogenesis has been postulated. D2 KO mice showed no impairment in sensorimotor tests, with only sensory impairment in an olfaction-dependent task. However, D2 KO mice showed proper procedural learning as well as learning in context (including remote memory), cue, and trace fear conditioning, Morris water maze, novel object recognition test, and in a multifunctional behavioral system-IntelliCages. D2 KO mice also demonstrated correct reversal learning. Our results suggest that adult brain neurogenesis is not obligatory in learning, including the kinds of learning where the role of adult neurogenesis has previously been strongly suggested.

Research paper thumbnail of Cognitive Abilities of Alzheimers Disease Transgenic Mice are Modulated by Social Context and Circadian Rhythm

Current Alzheimer Research, 2011

In the present study, we used a new training paradigm in the intelliCage automatic behavioral ass... more In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12-and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

Research paper thumbnail of Towards a computational model of learning and social interactions of mice in IntelliCage

BMC Neuroscience, 2013

Full list of author information is available at the end of the article

Research paper thumbnail of Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury

Behavioural Brain Research, 2011

Herein, we used a clinically-relevant model of 10 min cardiac arrest (CA) in Wistar rats. Histolo... more Herein, we used a clinically-relevant model of 10 min cardiac arrest (CA) in Wistar rats. Histological analyses of the ischemic brains of old rats showed significant atrophy of CA 1 sector of hippocampus (Nissl and NeuN stainings) corresponding with increase of glial fibrillary acidic protein expression. The longterm behavioral consequences of above manipulation producing global brain ischemia were assessed in young, middle-aged and old rats, i.e., 3-, 6-and 18-months post-treatment, respectively. In young animals no differences were found in the context-dependent memory in Fear Conditioning test. The most striking behavioral abnormalities were found in middle-aged rats (6 months post-ischemia). Ischemic rats showed hyperactivity and decreased level of anxiety in Open Field and problems with spatial learning and memory in a Novel Object Location test, T-maze and Morris Water Maze. In old animals, a decline of motor and cognitive functions was found not only in ischemic but also in sham/control ones. This study describes consequences of global brain ischemia in aging animals. contributed equally to this article.

Research paper thumbnail of Genetic models to study adult neurogenesis

Research paper thumbnail of Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction

Neurotoxicity research, 2008

GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the... more GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the brain. In the present study, glutamate transporter 1-deficient GLT1 homozygous (-/-) and heterozygous (+/-) mice were investigated with the intention that they may provide a model of hyperglutamatergic state resulting in various behavioral alterations. The GLT1 (-/-) mice had lower body and brain weight, mild neuronal loss in CA1 hippocampal region as well as focal gliosis and severe focal neuronal paucity in layer II of the neocortex. The short life-span of GLT1 (-/-) precluded us from systematic behavioral studies in these mice. In contrast, GLT1 (+/-) mice exhibiting a 59% decrease in GLT1 immunoreactivity in their brain tissue, showed no apparent morphological brain abnormalities, and their life-span was not markedly different from controls. Behaviorally, GLT1 (+/-) presented moderate behavioral alterations compared to their wildtype littermates, such as: mild sensorimotor impairmen...

Research paper thumbnail of Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 4, 2013

Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive l... more Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.

Research paper thumbnail of Kiryk Current Alzheimer Research 2011

In the present study, we used a new training paradigm in the intelliCage automatic behavioral ass... more In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12-and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

Research paper thumbnail of Genetic models to study adult neurogenesis

Acta biochimica Polonica, 2005

In the central nervous system (CNS) generation of new neurons continues throughout adulthood, whe... more In the central nervous system (CNS) generation of new neurons continues throughout adulthood, when it is limited to the olfactory bulb and hippocampus. The knowledge regarding the function of newly-generated neurons remains limited and is vigorously investigated using diverse approaches. Among these are genetically modified mice, most of them of knock-out type (KO). Results from 23 diverse KO mouse models demonstrate the importance of particular proteins (growth factors, nitric oxide synthases, receptors, cyclins/cyclin-associated proteins, transcription factors, etc.) in adult neurogenesis (ANGE) as well as separate it from developmental neurogenesis. These results bring us closer to revealing the function of newly generated neurons in adult brains.

Research paper thumbnail of Impaired rRNA synthesis triggers homeostatic responses in hippocampal neurons

Frontiers in Cellular Neuroscience, 2013

Research paper thumbnail of Impairment of adult brain neurogenesis does not promote depressive-like behavior

Frontiers in Behavioral Neuroscience, 1970

ABSTRACT Adult neurogenesis (ANGE) is the process of generation of new neurons in the brain of ad... more ABSTRACT Adult neurogenesis (ANGE) is the process of generation of new neurons in the brain of adult animals. Neuronal stem/precursor cells located in the subgranular zone of dentate gyrus (DG) and subventricular zone of the lateral ventricles proliferate and differentiate into mature neurons of the DG and olfactory bulb, respectively. Functional role of ANGE remains elusive, although it has been suggested to play an important role in the etiology of depression and its treatment with antidepressants. In our study we employed cyclin D2 gene knock-out (KO) mice showing approximately 10 times lower level of adult neurogenesis when compared to WT animals (Kowalczyk et al., J. Cell Biol., 2004). We have further characterized this deficit by demonstrating that KO mice show twice less astrocytes (GFAP-positive) when compared to WTs in the area of granular cell layer and hilus of the DG in the hippocampus formation. Furthermore, KO mice displayed a reduction of the apoptotic cells number (expressing active caspase-3) in analogous brain regions. Next, we have investigated whether the suppression of ANGE promotes the depressive-like behavior in KO mice when compared to WTs. We examined the initial depression level using a set of behavioral tests: tail suspension (TST), forced swimming (FST), nest building, novelty suppressed feeding, and anhedonic behavior test (using IntelliCage automated system). There was no significant effect of ANGE repression on KO mice behavior. We have also investigated whether the impairment of the adult brain neurogenesis alters the behavioral response of KO mice to antidepressants. Single injection of fluoxetine or imipramine (15 mg/kg) produced no difference in immobility between KO and WT animals in TST and FST. These result may suggest that ANGE suppression is rather a consequence than a cause of depressive behavior previously showed in animal models and human.

Research paper thumbnail of New hippocampal neurons are not obligatory for memory formation; cyclin D2 knockout mice with no adult brain neurogenesis show learning

Learning & Memory, 2009

The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to b... more The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs known for their side effects and the results obtained vary greatly. We used a novel approach, cyclin D2 knockout mice (D2 KO mice), specifically lacking adult brain neurogenesis to verify its importance in learning and memory. D2 KO mice and their wild-type siblings were tested in several behavioral paradigms, including those in which the role of adult neurogenesis has been postulated. D2 KO mice showed no impairment in sensorimotor tests, with only sensory impairment in an olfaction-dependent task. However, D2 KO mice showed proper procedural learning as well as learning in context (including remote memory), cue, and trace fear conditioning, Morris water maze, novel object recognition test, and in a multifunctional behavioral system-IntelliCages. D2 KO mice also demonstrated correct reversal learning. Our results suggest that adult brain neurogenesis is not obligatory in learning, including the kinds of learning where the role of adult neurogenesis has previously been strongly suggested.

Research paper thumbnail of Cognitive Abilities of Alzheimers Disease Transgenic Mice are Modulated by Social Context and Circadian Rhythm

Current Alzheimer Research, 2011

In the present study, we used a new training paradigm in the intelliCage automatic behavioral ass... more In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12-and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

Research paper thumbnail of Towards a computational model of learning and social interactions of mice in IntelliCage

BMC Neuroscience, 2013

Full list of author information is available at the end of the article

Research paper thumbnail of Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury

Behavioural Brain Research, 2011

Herein, we used a clinically-relevant model of 10 min cardiac arrest (CA) in Wistar rats. Histolo... more Herein, we used a clinically-relevant model of 10 min cardiac arrest (CA) in Wistar rats. Histological analyses of the ischemic brains of old rats showed significant atrophy of CA 1 sector of hippocampus (Nissl and NeuN stainings) corresponding with increase of glial fibrillary acidic protein expression. The longterm behavioral consequences of above manipulation producing global brain ischemia were assessed in young, middle-aged and old rats, i.e., 3-, 6-and 18-months post-treatment, respectively. In young animals no differences were found in the context-dependent memory in Fear Conditioning test. The most striking behavioral abnormalities were found in middle-aged rats (6 months post-ischemia). Ischemic rats showed hyperactivity and decreased level of anxiety in Open Field and problems with spatial learning and memory in a Novel Object Location test, T-maze and Morris Water Maze. In old animals, a decline of motor and cognitive functions was found not only in ischemic but also in sham/control ones. This study describes consequences of global brain ischemia in aging animals. contributed equally to this article.

Research paper thumbnail of Genetic models to study adult neurogenesis

Research paper thumbnail of Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction

Neurotoxicity research, 2008

GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the... more GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the brain. In the present study, glutamate transporter 1-deficient GLT1 homozygous (-/-) and heterozygous (+/-) mice were investigated with the intention that they may provide a model of hyperglutamatergic state resulting in various behavioral alterations. The GLT1 (-/-) mice had lower body and brain weight, mild neuronal loss in CA1 hippocampal region as well as focal gliosis and severe focal neuronal paucity in layer II of the neocortex. The short life-span of GLT1 (-/-) precluded us from systematic behavioral studies in these mice. In contrast, GLT1 (+/-) mice exhibiting a 59% decrease in GLT1 immunoreactivity in their brain tissue, showed no apparent morphological brain abnormalities, and their life-span was not markedly different from controls. Behaviorally, GLT1 (+/-) presented moderate behavioral alterations compared to their wildtype littermates, such as: mild sensorimotor impairmen...