Stefan Kasicki

Determination of information flow direction among brain structures by a modified directed transfer function (dDTF) method

A modification of directed transfer function-direct DTF-is proposed for the analysis of direct information transfer among brain structures on the basis of local field potentials (LFP). Comparison of results obtained by the analysis of simulated and experimental data with a new dDTF and DTF method is shown. A new measure to estimate direct causal relations between signals is defined. The present results demonstrate the effectiveness of the new dDTF method and indicate that the dDTF method can be used to obtain the reliable patterns of connections between various brain structures.

Information flow between hippocampus and related structures during various types of rat's behavior

The relationships among the CA1 field of hippocampus, the entorhinal-piriform area, the subiculum and the lateral septum were studied in various behavioral states in the rat. The EEG signals recorded simultaneously from chronically implanted electrodes were analyzed by means of a multichannel autoregressive (AR) model. Power spectra, ordinary, multiple and partial coherences, and directed transfer functions were calculated. The method of analysis which took into account all signals simultaneously, not pair-wise, made it possible to estimate the spectral characteristics and the directions of the EEG flow between structures. The pattern of the EEG activity propagation depended on the type of behavior, difficulty of the task performed by the animal, and the phase of the trial. Our results not only confirmed the existence of connections between analyzed structures, but also showed that these connections may have different strengths during various types of behavior.

Theta-like rhythm in depth EEG activity of hypothalamic areas during spontaneous or electrically induced locomotion in the rat.

Spontaneous locomotion performed by an awake rat is accompanied by synchronized activity (a theta rhythm) of the hippocampus (Hipp). Locomotion can also be induced by electrical stimulation of various sites within the brain. The effectiveness of electrical stimulation of the subthalamic locomotor region (SLR) and posterior hypothalamus (PH) in inducing locomotor movements has previously shown that they are parts of the system controlling locomotion. Thus, it was of interest to determine whether their electrical activity was correlated with the motor behavior, as it is in the Hipp. The experiments done here on chronic animals with electrodes implanted into the Hipp and hypothalamus showed that rhythmic depth EEG activity (theta-like) similar to that found in the Hipp is present in motor-positive hypothalamic areas during spontaneous locomotion. In addition, our results showed that movements induced by stimulation of various hypothalamic sites are also accompanied by theta-like activity in the Hipp and some hypothalamic areas. Thus, our results support the idea that the well-known and anatomically established connections between the Hipp and hypothalamus are active during locomotion. These connections may constitute a part of the system involved in the control of the motor behavior.

Differential effects produced by ketamine on oscillatory activity recorded in the rat hippocampus, dorsal striatum and nucleus accumbens

Previously, we showed that NMDA antagonists enhance high-frequency oscillations (130–180 Hz) in the nucleus accumbens. However, whether NMDA antagonists can enhance high-frequency oscillations in other brain regions remains unclear. Here, we used monopolar, bipolar and inverse current source density techniques to examine oscillatory activity in the hippocampus, a region known to generate spontaneous ripples (∼200 Hz), its surrounding tissue, and the dorsal striatum, neuroanatomically related to the nucleus accumbens. In monopolar recordings, ketamine-induced increases in the power of high-frequency oscillations were detected in all structures, although the power was always substantially larger in the nucleus accumbens. In bipolar recordings, considered to remove common-mode input, high-frequency oscillations associated with ketamine injection were not present in the regions we investigated outside the nucleus accumbens. In line with this, inverse current source density showed the greatest changes in current to occur in the vicinity of the nucleus accumbens and a monopolar structure of the generator. We found little spatial localisation of ketamine high-frequency oscillations in other areas. In contrast, sharp-wave ripples, which were well localized to the hippocampus, occurred less frequently after ketamine. Notably, we also found ketamine produced small, but significant, changes in the power of 30–90 Hz gamma oscillations (an increase in the hippocampus and a decrease in the nucleus accumbens).

Effects of strychnine on fictive swimming in the lamprey: evidence for glycinergic inhibition, discrepancies with model predictions, and novel modulatory rhythms

Abstract1.Inhibitory postsynaptic potentials (ipsps) produced by two classes of interneurons, CC (contralateral and caudal projecting) and lateral interneurons, were tested for strychnine sensitivity using paired intracellular recordings in the lamprey spinal cord. The ipsps were partially blocked by 0.2–0.5 μM strychnine and were completely blocked by 5 μM strychnine. Thus, the ipsps may be glycinergic.2.These interneurons are key participants in a proposed circuit model for fictive swimming. A connectionisttype computer simulation of the model demonstrated that the cycle period of the network increased with decreasing ipsp strength.3.Application of strychnine (0.1–0.5 μM) to the spinal cord during fictive swimming induced by an excitatory amino acid increased cycle period, consistent with previous reports, but at odds with stimulation predictions.4.Strychnine also produced slow rhythmic modulation of fictive swimming (period = 12 s) which maintained left-right alternation and rostral-caudal coordination. Auto- and cross-correlation analyses revealed that the slow modulation was present in a weaker form in most control preparations during fictive swimming.5.Since the proposed model for the swimming pattern generator in the lamprey spinal cord does not predict the observed speeding with strychnine, nor the slow modulatory rhythm, it appears to be deficient in its present formulation.

A systematic review of the effects of NMDA receptor antagonists on oscillatory activity recorded in vivo

Distinct frequency bands can be differentiated from neuronal ensemble recordings, such as local field potentials or electrocorticogram recordings. Recent years have witnessed a rapid acceleration of research examining how N-methyl-D-aspartate receptor (NMDAR) antagonists influence fundamental frequency bands in cortical and subcortical brain regions. Herein, we systematically review findings from in vivo studies with a focus on delta, theta, gamma and more recently identified high-frequency oscillations. We also discuss some of the current hypotheses that are considered to account for the actions of NMDAR antagonists on these frequency bands. The data emphasize a close relationship between altered oscillatory activity and NMDAR blockade, with both local and large-scale networks accounting for their effects. These findings may have fundamental implications for the psychotomimetic effects produced by NMDAR antagonists.

Local injection of MK801 modifies oscillatory activity in the nucleus accumbens in awake rats

Pharmacological blockade of NMDA receptors is used to model certain aspects of schizophrenia. It had been shown previously that ketamine dose dependently enhances high-frequency oscillations in the rodent nucleus accumbens, a structure implicated in schizophrenia. Here, the authors examined the effect of intra-accumbal and systemic administration of MK801 on delta, gamma and high-frequency oscillatory activity recorded in the nucleus accumbens of freely moving rats. In this study, rats were implanted with electrodes in the nucleus accumbens for chronic local field potential recording. Rats received either bilateral injections of MK801 (1 and 4 μg) or intraperitoneal injections of the drug (0.1 and 0.5 mg/kg). Saline was used as control in each instance. Both local and systemic injections significantly enhanced the power and frequency of high-frequency oscillations and caused an increase in the occurrence, duration and amplitude of high-frequency oscillatory bursts. In contrast, no effect or a decrease in the power of delta and gamma bands was observed following local or systemic administration of MK801, respectively. These findings suggest that the dominant change in oscillatory activity after administration of NMDA receptor antagonists affect high frequencies. Moreover, direct NMDA blockade in the accumbal circuitry is sufficient to generate increases in high-frequency oscillations. The presence of abnormal oscillatory activity in the accumbens may be associated with the psychomimetic effects of NMDA receptor antagonists.

Antipsychotic compounds differentially modulate high-frequency oscillations in the rat nucleus accumbens: a comparison of first- and second-generation drugs

Improved understanding of the actions of antipsychotic compounds is critical for a better treatment of schizophrenia. Abnormal oscillatory activity has been found in schizophrenia and in rat models of the disease. N-Methyl-D-aspartic acid receptor (NMDAR) antagonists, used to model certain features of schizophrenia, increase the frequency and power of high-frequency oscillations (HFO, 130-180 Hz) in the rat nucleus accumbens, a brain region implicated in schizophrenia pathology. Antipsychotics can be classified as first- and second-generation drugs, the latter often reported to have wider benefit in humans and experimental models. This prompted the authors to examine the pre- and post-treatment effects of clozapine, risperidone (second-generation drugs) and sulpiride and haloperidol (first-generation drugs) on ketamine and MK801-enhanced accumbal HFO. Both NMDAR antagonists increased HFO frequency. In contrast, clozapine and risperidone markedly and dose-dependently reduced the frequency of spontaneous and NMDAR-antagonist-enhanced HFO, whilst a moderate effect was found for sulpiride and a much weaker effect for haloperidol. Unexpectedly, we found reductions in HFO frequency were associated with an increase in its power. These findings indicate that modulation of accumbal HFO frequency may be a fundamental effect produced by antipsychotic compounds. Of the drugs investigated, first- and second-generation compounds could be dissociated by their potency on this measure. This effect may partially explain the differences in the clinical profile of these drugs.

Motor activity patterns in rat soleus muscle after neonatal partial denervation

In normal rats the development of organized patterns of hind limb movements takes place during the first three weeks of life. After removal of a part of the rat soleus muscles innervation in 5-day-old animals, the remaining motoneurones occupy a large peripheral field. The possibility that the development of the normal activity patterns of these motor units may be altered was studied. The EMG activity of the soleus muscles partially denervated at five days was compared to that of the contralateral unoperated muscles during spontaneous locomotion and induced reflex activity in animals at various ages. Like a normal soleus the partially denervated soleus developed with age a tonic activity pattern but the aggregate activity recorded from the partially denervated soleus was less than that in the control muscle. However, the amount of activity per motor unit was higher in the operated than in the control muscles, since these had only one-third to half of their normal complement of motor units. During locomotion both soleus muscles were activated like typical ankle extensors during the stance phase of the step cycle, but the burst duration of the operated muscle was significantly shorter. We conclude that partial denervation shortly after birth leads to an overall increase in activity of the remaining soleus motor units but does not drastically alter their temporal pattern of use during locomotion.

NMDA receptor antagonist-enhanced high frequency oscillations: Are they generated broadly or regionally specific?

Systemic administration of NMDA receptor antagonists, used to model schizophrenia, increase the power of high-frequency oscillations (130-180Hz, HFO) in a variety of neuroanatomical and functionally distinct brain regions. However, it is unclear whether HFO are independently and locally generated or instead spread from a distant source. To address this issue, we used local infusion of tetrodotoxin (TTX) to distinct brain areas to determine how accurately HFO recorded after injection of NMDAR antagonists reflect the activity actually generated at the electrode tip. Changes in power were evaluated in local field potentials (LFPs) recorded from the nucleus accumbens (NAc), prefrontal cortex and caudate and in electrocorticograms (ECoGs) from visual and frontal areas. HFO recorded in frontal and visual cortices (ECoGs) or in the prefrontal cortex, caudate (LFPs) co-varied in power and frequency with observed changes in the NAc. TTX infusion to the NAc immediately and profoundly reduced the power of accumbal HFO which correlated with changes in HFO recorded in distant cortical sites. In contrast, TTX infusion to the prefrontal cortex did not change HFO power recorded locally, although gamma power was reduced. A very similar result was found after TTX infusion to the caudate. These findings raise the possibility that the NAc is an important neural generator. Our data also support existing studies challenging the idea that high frequencies recorded in LFPs are necessarily generated at the recording site.