Responses In Cerebral Cortex Research Articles

Reflecting the causes of variability of EEG responses elicited by cerebellar TMS

Recently, Fong et al. published EEG responses in cerebral cortex elicited by cerebellar TMS (cbTMS) (Fong et al., 2023), which differ from our recently identified cbTMS-EEG responses (Gassmann et al., 2022). Fong et al. argued that this discrepancy is due to coil placement unsuitable for eliciting cerebellar brain inhibition (CBI) in our study. However, we reliably elicited CBI in our subjects. Consequently, this leads to a compelling discussion on possible reasons for the observed discrepancies in cbTMS-evoked EEG responses. Reliably measuring cbTMS-evoked EEG responses could become an important neurophysiological tool to test effective cerebellum-to-cortex connectivity.

Post-ischemic reorganization of sensory responses in cerebral cortex.

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats' forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex. The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

Microglia contributes to remyelination in cerebral but not spinal cord ischemia.

Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in gray matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion. Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance.

Contactless Assessment of Cerebral Autoregulation by Photoplethysmographic Imaging at Green Illumination.

Accurate and practical assessment of the brain circulation is needed to adequately estimate the viability of cerebral blood flow regulatory mechanisms in various physiological conditions. The objective of our study was to examine feasibility of the contactless green-light imaging photoplethysmography (PPG) for assessing cerebral autoregulation by revealing the dynamic relationships between cortical microcirculation assessed by PPG and changes in systemic blood pressure caused by visceral and somatic peripheral stimuli. In anesthetized male Wistar rats, the PPG video images of the open parietal cortex (either with unimpaired or dissected dura mater), electrocardiogram, and systemic arterial blood pressure (ABP) in the femoral artery were continuously recorded before, during and after visceral (colorectal distension) or somatic (tail squeezing) stimulation. In the vast majority of experiments with intact and removed dura mater, both spontaneous and peripheral stimulation-evoked changes in ABP negatively correlated with the accompanying alterations in the amplitude of pulsatile PPG component (APC), i.e., an increase of ABP resulted in a decrease of APC and vice versa. The most pronounced ABP and APC alterations were induced by noxious stimuli. Visceral painful stimulation in all cases caused short-term hypotension with simultaneous increase in cortical APC, whereas somatic noxious stimuli in 8 of 21 trials produced hypertensive effect with decreased APC. Animals with pressure 50-70 mmHg possessed higher negative cerebrovascular response rate of ABP-APC gradients than rats with either lower or higher pressure. Severe hypotension reversed the negative ratio to positive one, which was especially evident under visceral pain stimulation. Amplitude of the pulsatile PPG component probably reflects the regulation of vascular tone of cerebral cortex in response to systemic blood pressure fluctuations. When combined with different kinds of peripheral stimuli, the technique is capable for evaluation of normal and elucidation of impaired cerebrovascular system reactivity to particular physiological events, for example pain. The reported contactless PPG monitoring of cortical circulatory dynamics during neurosurgical interventions in combination with recordings of changes in other physiological parameters, such as systemic blood pressure and ECG, has the appealing potential to monitor viability of the cortex vessels and determine the state of patient’s cerebrovascular autoregulation.

Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

Modern methods of diagnosing addiction to psychoactive substances: neurophysiological aspects

Objective:The study of the features of the higher mental functions of the brain in patients suffering from addiction to psychoactive substances is very important for narcology. It is necessary not only to uncover the mechanisms of addiction, a complete understanding of the neurophysiological processes that determine the nature of the development and severity of the disease, but also to solve practical problems related to the development of treatment methods and the implementation of preventive measures.Method:In the study of patients, a specially designed map was used containing information on the hereditary and demographic characteristics, on the course of the disease, as well as on the socio-cultural status of patients. To determine the functional state of cortical activity in the process of perception of unconscious signals, a special technique was used. The obtained results were subjected to dispersive analysis and the significance of differences was calculated according to Student’s t-criterion.Results:An analysis of premorbid personality traits made it possible to establish the prevalence of instability, pathological conformity, and hysteroidal features in patients. It should be noted that a large percentage of the surveyed had a hereditary burden of alcoholism, mainly in the line of the father. Curiosity, passive submission, imitation of friends were among the motives of the first drug use. All patients in the process of addiction formed the following features: increased excitability, increasing effective disorders (depression, dysphoria), aggravated by exacerbation of craving for the drug, a decline in morals and ethics (egoism, deceit, indifference to one’s fate, hedonism, loss of sense of duty), disorders of the emotional-volitional sphere (emotional instability, hypersensitivity, vulnerability).Conclusion:The analysis of the duration of latent periods and magnitude of the amplitudes of the late positive R3OO wave in patients with heroin addiction revealed clear differences between the data obtained upon presentation of an unconscious neutral and motivationally significant word. Patients who use psychoactive substances, using the method of recording induced potentials of the brain, which is a sensitive indicator of the activity of brain structures in relation to the substance used, revealed a clear diffuse activation of the cerebral cortex in response to an unconscious verbal stimulus related to the motivation prevailing in patients, in particular to “heroin”. Such activation, as well as the difficult dying out of the developed reactions to an unconscious stimulus, indicate certain neurophysiological foundations of the mechanism underlying the changes in the motivational sphere and the stability of the pathological craving for the psychoactive substance.

Activation of Multimodal Areas in the Human Cerebral Cortex in Response to Biological Motion Sounds

Functional magnetic resonance imaging (fMRI) was used to investigate activation of the multimodal areas in the cerebral cortex–supramarginal and angular gyri, precuneus, and middle temporal visual cortex (MT/V5)–in response to motion of biologically significant sounds (human footsteps). The subjects listened to approaching or receding footstep sounds during 45 s, and such stimulation was supposed to evoke auditory adaptation to biological motion. Listening conditions alternated with stimulation-free control. To reveal activity in the regions of interest, the periods before and during stimulation were compared. Most stable and voluminous activation was detected in the supramarginal and angular gyri, being registered for all footstep sound types–approaching, receding and steps in place. Listening to human approaching steps activated the precuneus area, with the volume of activation clusters varying considerably between subjects. In the MT/V5 area, activation was revealed in 5 of 21 subjects. The involvement of the tested multimodal cortical areas in analyzing biological motion is discussed.

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex.

The cerebral response to fetal asphyxia is characterized by an upregulation of nucleic acid and chromatin modification processes, as well as a downregulation of metabolic processes at 1h post-umbilical cord occlusion (UCO). Twenty-four hours post UCO, there was an upregulation of metabolic processes and protein modifications. UCO did not alter bacterial gene expression levels, nor did it produce a robust inflammatory response compared to maternal hypoxia. The administration of ketamine produced minimal effects on the fetal response to UCO in the cerebral cortex. Umbilical cord occlusion (UCO) is known to cause neurological disorders in the neonate. Previously, we have reported that hypoxic hypoxia (HH) stimulates the appearance of bacteria in the fetal brain and upregulates the expression of inflammatory markers in fetal cerebral cortex (CTX) and also that ketamine attenuates these responses. In the present study, we aimed to test the hypothesis that UCO, similar to HH, produces an inflammatory response in the fetal CTX and also that treatment with ketamine reduces these effects. In chronically instrumented fetal sheep (∼125days), 30min of partial UCO decreased fetal levels by ∼50%. Half of the fetuses received ketamine (3mgkg-1 ) 10min prior to UCO (n=4 per group). Fetal brains were collected 1 and 24h after the experiment and mRNA was extracted and hybridized for microarray analyses. Differentially-expressed genes were analysed for significant association with gene ontologies and pathways. After 1h, UCO upregulated nucleic acid processing and chromatin modification and downregulated metabolic processes compared to control. After 24h, UCO upregulated metabolic and protein modification processes. Ketamine produced minimal effects. UCO did not alter the abundance of bacterial DNA in fetal brain, nor did it upregulate inflammation pathways compared to HH. We conclude that UCO produced time-dependent responses that did not include bacterial invasion or upregulation of inflammation pathways in fetal CTX. This contrasts with the response to HH, which resulted in the appearance of bacteria in the CTX and upregulated inflammation pathways. These responses in fetal CTX to oxygen deprivation are therefore modified by the maternal or placental response to the stimulus.

Evaluation of Neurotoxicity of Multiple Anesthesia in Children Using Visual Evoked Potentials.

Objectives:Anesthetic applications may cause increased neuronal damage in infants and children. Commonly cognitive or learning disability tests were used to investigate the neurological progress in children. Visual Evoked Potential is a gross electrical signal generated by the occipital regions of the cerebral cortex in response to visual stimulation and an objective assessment of brain function. In this study, to acquire more objective results, Visual Evoked Potential responses of children who had multiple exposures to anesthesia during the treatment of corrosive esophagitis were compared to children who have never received anesthesia before.Methods:In this prospective, single-blinded, randomized, controlled study, 25 children, who were admitted to our pediatric surgery clinic because of corrosive esophagitis and who received general anesthesia more than 15 times composed Group-P; 25 children, who admitted to our well-child-clinic and who had never received anesthesia before consisted Group-C. The flash and pattern VEP responses of both groups were measured at the electrophysiology laboratory without any anesthetic drug application. The VEP responses of children in Group-P were recorded at least three days after the last exposure to anesthesia.Results:Latencies and amplitudes of the N2 and P2 components of the pattern and flash VEP responses were statistically significantly different between the two groups (p=0.000).Conclusion:This study shows that in children who had repeated anesthetic applications VEP parameters are significantly altered. We believe that VEP responses may be a reliable objective criterion for the evaluation of anesthesia neurotoxicity.

Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice.

The effects of Ulinastatin on the inflammatory response in cerebral cortex of Wistar rats after cardiopulmonary resuscitation

Objective To evaluate the effects of Ulinastatin (UTI) on the expressions of TNF-α,IL-6 and neurons apoptosis in cerebral cortex of rats after cardiopulmonary resuscitation (CPR). Methods Thirty-six healthy male adult Wistar rats were induced ventricular fibrillation untreated for 7 min and then received CPR. The animals were infused UTI 100 000 U/ kg or phosphate-buffered solution (PBS) at once after ROSC. At 2,4 and 8 h after ROSC,cerebral cortex were removed to determine the mRNA expressions and levels of TNF-α protein and IL-6 protein,the translocation ratio of NF-κB p65 from cytoplasm to nucleus and the apoptotic neurons. Results The plasma levels of TNF-α(ng/ mL) in animals of UTI group were (17.7 ±1.4), (21.9 ±2.1) and (17.1 ±0.6) at 2,4 and 8 h after ROSC respectively,and significantly lower than those in PBS group at the given intervals. Mean while,the levels of IL-6 (ng/ mL) were (208.9 ±14.1), (281.5 ±25.9) and (251.8 ±15.3) at 2,4 and 8 h after ROSC respectively in animals of UTI group,and lower than those in PBS group. The expressions of TNF-α mRNA and IL-6 mRNA and protein levels of TNF-α and IL-6 in UTI group were both lower than those in PBS group at given intervals, respectively. The translocation ratio of NF-κB p65 from plasma to nucleus in PBS group at each given interval after ROSC was significantly higher than that in UTI group. The number of viable neurons in cerebral cortex in UTI group was higher than that in PBS group,while the number apoptosis neurons was fewer in UTI group. Conclusions UTI attenuated the general inflammatory response after ROSC in rat,decreased the activation of NF-κB pathway,and subsequently attenuated the expression of TNF-α and IL-6,and finally decreased the neurons apoptosis. Key words: Cardiopulmonary resuscitation; Ulinastatin; Inflammatory response; Cerebral cortex; Wistar rat

Arterial dilation in the parenchyma of the cerebral cortex in response to stimulation of the nucleus basalis of Meynert measured by two-photon microscopy

Arterial dilation in the parenchyma of the cerebral cortex in response to stimulation of the nucleus basalis of Meynert measured by two-photon microscopy

Differential Conserted Activity Induced Regulation of Nogo Receptors (1–3), LOTUS and Nogo mRNA in Mouse Brain

Nogo Receptor 1 (NgR1) mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity.

Time-Dependent Modulation of Mitogen Activated Protein Kinases and AKT in Rat Hippocampus and Cortex in the Pilocarpine Model of Epilepsy

The epileptogenesis may involve a variety of signaling events that culminate with synaptic reorganization. Mitogen-activated protein kinases (MAPKs) and AKT may be activated by diverse stimulus including neurotransmitter, oxidative stress, growth factors and cytokines and are involved in synaptic plasticity in the hippocampus and cerebral cortex. The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. We analyze the phosphorylation profile of MAPKs (ERK1/2, p38(MAPK), JNK1/2/3) and AKT by western blotting in the hippocampus (Hip) and cortex (Ctx) of male adult wistar rats in different periods, after pilocarpine induced status epilepticus (Pilo-SE) and compared with control animals. Biochemical analysis were done in the Hip and Ctx at 1, 3, 12h (acute period), 5days (latent period) and 50days (chronic period) after Pilo-SE onset. Hence, the main findings include increased phosphorylation of ERK1 and p38(MAPK) in the Hip and Ctx 1 and 12h after the Pilo-SE onset. The JNK2/3 isoform (54kDa) phosphorylation was decreased at 3h after the Pilo-SE onset and in the chronic period in the Hip and Ctx. The AKT phosphorylation increased only in the Hip during the latent period. Our study demonstrates, in a systematic manner, the profile of MAPKs and AKT modulation in the hippocampus and cerebral cortex in response to pilocarpine. Based in the role of each signaling enzyme is possible that these changes may be related, at least partially, to modifications in the intrinsic neuronal physiology and epileptogenic synaptic network that appears in the MTLE-HS.

Evoking Potentials from the Brain (P04.009)

Objective: To present the history of discovery of evoked potentials by reviewing the original publications of Caton, Beck, Dawson and Jewett. Background Caton9s publications revealed that unstimulated cerebral cortex had a positive charge and stimulation of an animal9s limb could produce waves of negative cortical currents in contralateral motor cortex. Design/Methods: Review of publications of Caton, Beck, Dawson and Jewett. Results: Richard Caton (1842-1926) discovered somatosensory evoked responses in 1875 Caton demonstrated fluctuations of a galvanometer connected to electrodes on exposed surfaces of rabbits9 cerebral cortex in response to stimulation of hind paws. Caton noted negative current fluctuations from occipital cortex after he shined light into retinas of rabbits. Adolph Beck in 1890 claimed primacy of discovery for similar observations. In 1947 Charles Dawson (1912-1983) superimposed amplified multiple cortical somatosensory evoked responses (SER) on a screen of an oscilloscope improving signal-to-noise ratio (SNR) of the SER. In 1954 Dawson developed the signal averager (SA) to further improve SNRs. Dawson9s SA consisted of a rotating switch driven by a motor that fed each individual scalp response to a single median nerve stimulus into 1 of 62 condensers. The SA serially discharged each condenser into an amplifier connected to a storage oscilloscope. Dawson noted that the superimposed SER had a onset latency of 28 ms. Dawson proved that SA could eliminate EEG waves not related to the stimulus. Dawson9s median SERs resembled modern cortical SERs. Conclusions: Caton should be credited as discoverer of evoked responses. Dawson should be considered founder of human evoked potentials research, because his averaging technique extracted the evoked potential. Disclosure: Dr. Fine has received personal compensation for activities with Slocum-Dickson Clinic. Dr. Fine holds stock and/or stock options in Bristol Myers-Squibb, Eli Lilly, Pfizer, and Johnson & Johnson. Dr. Riggins has nothing to disclose. Dr. Farooq has nothing to disclose.

Sustained Decrease and Remarkable Increase in Red Blood Cell Velocity in Intraparenchymal Capillaries Associated With Potassium‐Induced Cortical Spreading Depression

To examine changes in red blood cell (RBC) velocity in intraparenchymal capillaries of rat cerebral cortex in response to KCl-induced cortical spreading depression (CSD). In isoflurane-anesthetized rats, the velocity of fluorescently labeled RBCs flowing in capillaries in layer I was measured with a high-speed camera laser-scanning confocal fluorescence microscope, with simultaneous monitoring of DC potential, the electroencephalogram (EEG), partial pressure of oxygen (PO(2) ), and cerebral blood flow (CBF). After KCl application, a transient deflection of DC potential (i.e., CSD) repeatedly appeared concomitantly with depression of EEG, and was propagated in the distal direction. PO(2) transiently decreased and CBF was slowly elevated. The frequency distribution of RBC velocity was shifted downward during CSD and was still low after the passage of CSD. When we observed RBC velocity in 38 individual capillaries, 10 capillaries exhibited slowed-down RBC during CSD and RBC velocity remained low in 2 even after the passage of CSD. On the other hand, RBCs with moderately (<3 mm/sec) or remarkably (>3 mm/sec) increased velocities were seen in 10 and 5 capillaries, respectively. CSD-induced excitation of neurons may sustainably decrease or greatly increase RBC velocity in capillaries.

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

The neurosteroid allopregnanolone (ALLO) or 3α-OH-5α-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3β position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3β-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3β-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3β-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3β-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3β-steroids can act as positive GABA A receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3β-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.

Electrographic Correlates of Adequate and Erroneous Responses Evoked by Conditioned Signals of Different Functional Signs During Operant Learning in Dogs

Power spectra over the frequency range 1-225 Hz in short-term (less than 1 sec) EEG reactions arising in different areas of the cerebral cortex in response to presentation of differential signals were investigated in dogs during operant feeding behavior in conditions of both adequate and erroneous responses. The energy levels of these reactions decreased several-fold as compared with responses to positive signals, mainly because of frequencies in the high-frequency range (90-225 Hz), where power was greater than not only the traditional range of 1-30 Hz, but also the gamma range of 30-80 Hz. The frequency composition of EEG reactions in adequate responses was determined by a series of discrete frequency subgroups belonging predominantly to the high-frequency band. In erroneous reactions, the discrete structure of the corresponding EEG reactions was lost.

Changes in the volume of the intercellular space of the cerebral cortex in conditions of peripheral stimulation in rats.

Changes in the volume of the intercellular space of the rat cerebral cortex in response to peripheral repetitive stimulation were studied. The volume of the intercellular space and its changes were assessed by a modification of the four-electrode impedance method. The results suggest that evoked electrical activity in the cerebral cortex was accompanied by 3-5% decreases in the volume of the intercellular space.

Central nervous system prostaglandin endoperoxide synthase-1 and -2 responses to oestradiol and cerebral hypoperfusion in late-gestation fetal sheep.

Previous work in this laboratory has demonstrated that cerebral hypoperfusion increases the expression of prostaglandin endoperoxide synthase-2 (PGHS-2) in ovine fetal brain regions. Endogenously produced prostaglandins, in turn, partially mediate the fetal hypothalamus- pituitary-adrenal (HPA) axis response to arterial hypotension. In separate experiments, we have found that oestradiol stimulates fetal HPA axis activity. The present experiments were designed to test the hypothesis that oestradiol increases the expression of PGHS isoforms, and that oestradiol augments the PGHS response to cerebral hypoperfusion. Sixteen fetal sheep of known gestational ages (124-128 days' gestation at the time of study) were subjected to chronic catheterization and implantation of extravascular occluder around the brachiocephalic artery. Eight fetuses were subjected to subcutaneous implantation of a pellet containing 17beta-oestradiol (release rate 5 mg (21 days)-1). Brachiocephalic occlusion (BCO) stimulated adrenocorticotropin (ACTH), cortisol and arginine vasopressin (AVP) secretion, responses that were augmented by oestradiol. One hour after the beginning of a 10 min period of BCO, PGHS-1 mRNA was increased in fetal brainstem and hypothalamus, and PGHS-2 mRNA was increased in fetal brainstem. Oestradiol, by itself, increased the abundance of PGHS-2 mRNA in brainstem and cerebellum, and augmented the PGHS-2 mRNA response to BCO in brainstem. In contrast, oestradiol had no significant effect on the abundance of PGHS-1 mRNA in any brain region. PGHS-1 and PGHS-2 protein levels did not reflect the changes in the respective mRNAs. The abundance of both proteins was increased in cerebral cortex in response to BCO, and the abundance of PGHS-2 protein was increased by both oestradiol and BCO in the hippocampus. The results of this study confirm and extend the results of our previous studies, demonstrating an effect of cerebral hypoperfusion on the expression of both isoforms of PGHS. We conclude that oestradiol increases the expression of PGHS-2 in specific fetal brain regions, and that there is an interaction between oestradiol and BCO in the control of PGHS-2 expression in the fetal brainstem. We expect that at later time-points, the changes in mRNA would be followed by similar changes in enzyme abundance at the protein level. We speculate that at least a part of the effect of oestradiol on fetal HPA axis function is mediated by an interaction between oestradiol and prostaglandin biosynthesis in the fetal brain.