LABORATORY OF LIMBIC SYSTEM

| Head: Stefan KASICKI, Ph.D., D.Sc. E-mail: s.kasicki@nencki.gov.pl Staff: Paweł BOGUSZEWSKI, M.Sc. Anna KORZENIEWSKA-JANISZEWSKA, M.Sc., Krystyna MIŁOSZ Jolanta ZAGRODZKA, Ph.D., D.Sc. Ph.D. Students: Małgorzata BASZCZAK, M.Sc. Paweł BORATYŃSKI, M.Sc

Laboratory of Limbic System was founded by Prof. Elżbieta Fonberg, prominent and well-known scientist in the area of neurophysiology of emotions and motivation. This line of research is still continued by Jolanta Zagrodzka and her collaborators. After a long period of work on dogs and cats, currently various aspects of emotional behavior are studied in rats, with the use of ethopharmacological approach concomitantly with biochemical analysis and recording of local field potentials. Pavlovian aversive conditioning and autonomic correlates of behavior (heart rate and diaphragm EMG activity) are used as well.

Recently the research is focused mainly on the brain defensive system with special interest paid to mechanisms of fear, anxiety and aggressive behavior. The series of experiments was done on rats confronted with stressogenic stimuli in order to determine the possible interactions between different neurotransmiters’ activity in correlation with behavioral alterations (9-11). In other work it was found that experimentally evoked affective states, i.e. fear, anxiety and inhibition of fear elicit characteristic pattern of ultrasound vocalization changes. Application of selected pharmacological agents allowed dissociating their target of action as directed to the anxiety level or learned responses to the stimuli of danger or safety (2).

Emotional changes related to age are investigated in combined behavioral and biochemical study. With the use of factor analysis motivational factors influencing spontaneous behavior in open field, elevated plus maze and social interactions test were identified in young and old animals. It has been demonstrated that, in addition to the decrease of motor activity, old rats differ quantitatively and qualitatively from young individuals in emotional and social behavior (1). Currently, the electrophysiological correlates of the differences in emotional reactivity between RHA and RLA rats are studied.

The second main topic of the research in the laboratory was the movement control, started by Dr. Zofia Afelt and continued by Kasicki and his coworkers. It is well known that limbic and motor systems are associated anatomically and functionally, and locomotion is a major component of food procurement, escape and other motivational/adaptive behaviors. One line of experiments was designed for analysis of theta rhythm recorded in hippocampus and hypothalamic area during locomotion (7, 8). The conclusion of the papers was that the theta rhythm frequency may depend not only on the speed of locomotion but also on the rat’s motivational-emotional state, associated with locomotion performed by the animal.

Affective processes occurring in the limbic structures gain access to the motor structures, initializing and shaping necessary action. The nucleus accumbens is considered a nodal point, through which this access is performed. The limbic-motor integration was studied by analysis of local field potentials (LFP) recorded from n. accumbens, basolateral n. of amygdala, ventral subiculum and subpallidal area in freely moving rats, during locomotor tasks in various behavioral situations. Analysis of partial coherences showed that the strength of connections between structures is sensitive to changes in both motor and emotional aspects of behavioral situation. (5). A new method (directed Direct Transfer Function) enables obtaining the reliable pattern of connections between various brain structures. The results demonstrate the effectiveness of the new dDTF method and indicate that the dDTF method can be used to obtain patterns of information flow between investigated structures (5, 6).

The influence of emotional state on hippocampal LFP activity is analyzed in another experimental paradigm, which enables studying the fear and relief from it. Partially restrained rats, implanted with chronic electrodes, are put to the Pavlovian aversive conditioning procedure, during which the LFPs are recorded. Preliminary results clearly demonstrate differentiation of hippocampal activity in opposite emotional states.

Recently the scientific interests of the laboratory team have spread out – the neuronal mechanisms of interactions between neurons are studied in electrophysiological experiments on thalamo-cortical slices and in modeling experiments. In in vitro experiments the organization of mutual connections between neurons in layers V and VI of barrel cortex and neurons in Po nucleus and ventrobasal complex of thalamus is studied, using intra- and extracellular recording. The experiments will also examine the possibility to induce long-term potentiation in neurons of layer V and VI of barrel cortex. Simulation studies use a realistic model neuron constructed in a MATLAB/SIMULINK environment. The model will be used for analysis of neural networks responsible for rhythm generation (e.g. locomotion), and mechanisms influencing synaptic plasticity.

Experiments investigating various aspects of plasticity of motor system were performed in collaboration with U. Sławińska (14, 15). Analysis of activity of spinal neurons in the lamprey’s spinal cord was done in collaboration with J. Buchanan (12, 13).

Selected publications:

1. Boguszewski P, Zagrodzka J (2002) Emotional changes related to age in rats - a behavioral analysis. Behav Brain Research 133(2):323-32.

2. Jelen P, Soltysik S, Zagrodzka J. (2003) 22-kHz ultrasonic vocalization as an index of anxiety but not fear: behavioral and pharmacological modulation of affective state. Behav Brain Research 141(1):63-72.

3. Jelen P, Zagrodzka J (2001) Heart rate changes in partially restrained rats during behaviorally and pharmacologically evoked emotional states. Acta Neurobiol Exp 61(1):53-67.

4. Korzeniewska A, Kasicki S, Kaminski M, Blinowska KJ (1997) Information flow between hippocampus and related structures during various types of rat's behavior. J Neurosci Methods 73(1):49-60.

5. Korzeniewska A, Kasicki S, Zagrodzka J (1997) Electrophysiological correlates of the limbic-motor interactions in various behavioral states in rats. Behav Brain Research 87(1):69-83.

6. Korzeniewska A, Mańczak M, Kamiński M, Blinowska KJ, Kasicki S (2003) Determination of information flow direction among brain structures by a modified Directed Transfer Function (dDTF) method. J Neurosci Methods 125(1-2):195-207.

7. Slawinska U, Kasicki S (1995) Theta-like rhythm in depth EEG activity of hypothalamic areas during spontaneous or electrically induced locomotion in the rat. Brain Research 678(1-2):117-26.

8. Slawinska U, Kasicki S (1998) The frequency of rat's hippocampal theta rhythm is related to the speed of locomotion. Brain Research 796(1-2):327-31.

9. Zagrodzka J (1995) Responsiveness to environmental stimuli after destruction of the locus coeruleus noradrenergic system. Human Psychopharmacology 10:467-73.

10. Zagrodzka J, Romaniuk A, Wieczorek M, Boguszewski P (2000) Bicuculline administration into ventromedial hypothalamus: effects on fear and regional brain monoamines and GABA concentrations in rats. Acta Neurobiol Exp 60(3):333-43.

11. Zagrodzka J, Wieczorek M, Romaniuk A (1994) Social interactions in rats: behavioral and neurochemical alterations in DSP-4-treated rats. Pharmacology, Biochemistry and Behavior 49(3):541-8.

Publications in collaboration:

12. Buchanan JT, Kasicki S (1999) Segmental distribution of common synaptic inputs to spinal motoneurons during fictive swimming in the lamprey. J Neurophysiology 82(3):1156-63.

13. Buchanan JT, Kasicki S (1995) Activities of spinal neurons during brain stem-dependent fictive swimming in lamprey. J Neurophysiology 73(1):80-7.

14. Slawinska U, Kasicki S (2002) Altered electromyographic activity pattern of rat soleus muscle transposed into the bed of antagonist muscle. J Neuroscience 22(14):5808-12.

15. Slawinska U, Tyc F, Kasicki S, Navarrete R, Vrbova G (1998) Time course of changes in EMG activity of fast muscles after partial denervation. Exp Brain Research 120(2):193-201.