Corticoliberin Protects Neurons from the Negative Influences of “Dysfunctins” in Living Olfactory Cortex Slices

The protective effects of corticoliberin on living rat olfactory cortex slices during perfusion with dysfunctins extracted from cerebrospinal fluid of drug addicts were studied. Isolated perfusion of slices with medium containing dysfunctins led to irreversible suppression of the amplitude of individual components of focal potentials induced by electrical stimulation of the lateral olfactory tract. The maximum level of depression was seen for the AMPA and NMDA components of EPSP. Preliminary perfusion of slices with medium containing corticoliberin (100 nM) for 15 min partially, and for 30 min completely protected processes mediated by activation of AMPA and NMDA receptor mechanisms from the negative influences of dysfunctins. It is suggested that corticoliberin can induce its protective effects either via its own specific receptors or non-specifically via glutamate receptors. It is also possible that both of these mechanisms act in combination.     

Reverberation of Excitation in Living “Hippocampal Formation–Entorhinal Cortex” Slices from Rats. Optical Recording

A vital potential-dependent dye was used to conduct optical recording of the electrical activity of the hippocampal formation in living slices of the rat brain including the hippocampal formation and the entorhinal cortex. These studies showed that single electrical stimuli applied to the entorhinal cortex, subiculum, and dentate gyrus produced responses in which waves of excitation passed across the hippocampal formation sequentially from the dentate gyrus, through CA3, to the CA1 field of the hippocampus. When GABAergic inhibition was partially blocked with picrotoxin, the first wave of excitation was immediately followed by several further waves in all zones of the hippocampal formation, with a constant shift in latency, which increased from the dentate gyrus to CA3 and CA1. Reverberation of excitation in the hippocampal formation-entorhinal cortex structure is regarded as the most probable cause for the appearance of these sequences of waves.     

Involvement of the Hypothalamic Nuclei in Forming Object–Place Associations in Neurons of Hippocampal Field CA2 (a hypothetical mechanism)

Neuroscience and Behavioral Physiology - A possible mechanism for the formation of representations of object–place associations in hippocampal neurons based on plastic rearrangements of the...     

Relationship between Long-Term Potentiation and the Initial Properties of CA3–CA1 Synapses: Importance of the Effects of External Factors on Hippocampal Synaptic Plasticity for Studies

Neuroscience and Behavioral Physiology - The phenomenon of long-term potentiation (LTP) is used for studies of the effects of various factors on the long-term plasticity of synapses in health and...     

The Development of GABA-containing Neurons in the Broca''''s Area of Human Fetus

Prenatal development of GABA-containingneurons in the Broca's area of human fetusranging in age from 17 weeks to full-termnewborn infant were studied by means ofGABA immunocytochemistry.The GABA-con-taining neurons were found in marginal layer,cortical plate,intermediate zone and subventri-     

Excitation Waves Returning to the Hippocampus via the Entorhinal Cortex Can Reactivate Populations of “Trained” Field CA1 Neurons during Deep Sleep

It is suggested that information on new stimuli from the neocortex is transmitted to the hippocampus, where temporal traces persist in the form of mosaics of modified synapses. During sleep, populations of neurons storing these traces are reactivated and return the information required for consolidation of a permanent memory trace to the neocortex. A possible mechanism for the reactivation of “trained” hippocampal neurons during memory consolidation consists of the reverberation of excitation in the neuron circuits linking the hippocampus and entorhinal cortex. Our studies in rats included recording of responses in hippocampal field CA1 to stimulation of Schaffer collaterals with potentiated synapses during waking and sleep. During deep sleep, discharges of field CA1 neurons were followed by waves of excitation which passed through the entorhinal cortex and reached the hippocampus and dentate gyrus via fibers of the perforant path, evoking neuron discharges in the latter. Repeated neuron discharges in field CA1 occurred on interaction of the early excitation wave returning directly via perforant path fibers and the late wave returning via Schaffer collaterals, not via the trisynaptic path via the dentate gyrus and hippocampal field CA3 but probably via field CA2.     

A Possible Mechanism for the Dopamine-Evoked Synergistic Disinhibition of Thalamic Neurons Via the “Direct” and “Indirect” Pathways in the Basal Ganglia

The mechanism of synaptic plasticity which we have previously proposed for striatal spiny neurons, along with published data on the predominance of dopamine-sensitive D1/D2 receptors on strionigral/striopallidal neurons, was used as the basis to propose the hypothesis that the induction of long-term potentiation/depression of the efficiency of the cortical inputs to these cells may result from the excitatory/inhibitory actions of dopamine on the activity of the neurons originating the direct and indirect pathways through the basal ganglia. Thus, the action of dopamine increases disinhibition of thalamic neurons via the direct pathway and decreases their inhibition via the indirect pathway. Both effects lead to increases in the activity of thalamic cells and in the activity of the efferent neocortical neurons which they excite. The actions of dopamine on striosomal neurons, which mainly have D1 receptors, may also be to induce long-term potentiation of cortical inputs. This effect should lead to increased inhibition of dopaminergic cells and decreases in their dopamine release, which may promote the maintenance of a stable dopamine concentration in the cortex-basal ganglia-thalamus-cortex neural network.     

Return of Excitatory Waves from Field CA1 to the Hippocampal Formation Is Facilitated after Tetanization of Schäffer Collaterals during Sleep

Current concepts hold that during learning in waking animals, new information is transmitted from the neocortex to the hippocampus, where it leaves a temporary trace in the form of a mosaic of modified synapses. During sleep, reactivation of the neuron population initially activated by the new stimulus has the result that this information is returned to the neocortex, ensuring consolidation of a permanent memory trace. Exchange of information between the neocortex and hippocampal formation is mediated mainly by the entorhinal cortex, whose internal connections, in principle, allow “messages” from the output of the hippocampal formation to return to its inputs. Our experiments in awake and sleeping rabbits demonstrated that waves of excitation can return to hippocampal field CA1 and the dentate gyrus via fibers of the perforant path, these waves having initially entered field CA1 via potentiated synapses of Sch?ffer collaterals; during sleep, re-entrant waves of excitation reach a maximum and have a high probability of evoking discharges of dentate gyrus neurons. Thus, the new stimulus, potentiating synaptic connections in the hippocampus and, probably, the entorhinal cortex during waking, create conditions for reactivation of the corresponding hippocampal neuron populations during sleep by waves of excitation returning via the entorhinal cortex.     

Interferon-γ Prevents Death of Bystander Neurons during CD8 T Cell Responses in the Brain

T cells restricted to neurotropic viruses are potentially harmful as their activity may result in the destruction of neurons. In the Borna disease virus (BDV) model, antiviral CD8 T cells entering the brain of infected mice cause neurological disease but no substantial loss of neurons unless the animals lack interferon-γ (IFN-γ). We show here that glutamate receptor antagonists failed to prevent BDV-induced neuronal loss in IFN-γ-deficient mice, suggesting that excitotoxicity resulting from glutamate receptor overstimulation is an unlikely explanation for the neuronal damage. Experiments with IFN-γ-deficient mice lacking eosinophils indicated that these cells, which specifically accumulate in the infected brains of IFN-γ-deficient mice, are not responsible for CA1 neuronal death. Interestingly, BDV-induced damage of CA1 neurons was reduced significantly in IFN-γ-deficient mice lacking perforin, suggesting a key role for CD8 T cells in this pathological process. Specific death of hippocampal CA1 neurons could be triggered by adoptive transfer of BDV-specific CD8 T cells from IFN-γ-deficient mice into uninfected mice that express transgene-encoded BDV antigen at high level in astrocytes. These results indicate that attack by CD8 T cells that cause the death of CA1 neurons might be directed toward regional astrocytes and that IFN-γ protects vulnerable CA1 neurons from collateral damage resulting from exposure to potentially toxic substances generated as a result of CD8 T cell-mediated impairment of astrocyte function.Controlling viral infections in the central nervous system is a very demanding task for the immune system as there is a substantial risk of collateral damage.¹ It is often difficult to assess the extent of damage caused by the antiviral immune response to nonrenewable cells in the brain. The reason for this difficulty is that the cytopathic activities of viruses and immune cells do not necessarily result in distinct pathologies. In experimental settings, the complexity of the system can be reduced if model viruses are used that have adopted noncytolytic replication strategies. A suitable pathogen for studying these issues is Borna disease virus (BDV).BDV can replicate in neurons and other cell types of the central and peripheral nervous system of mice and other mammals without damaging the host cells.^2,3 The noncytotoxic nature of BDV was most convincingly demonstrated in MRL/MpJ (MRL) mice lacking functional alleles of the β2-microglobulin gene, which, as a consequence, lack mature CD8 T cells. Unlike wild-type MRL mice that frequently develop fatal neurological disease after infection with BDV, mutant MRL mice lacking mature CD8 T cells are completely resistant to BDV-induced disease although the virus replicates to very high levels in the brain of such mice.⁴ Neurological disease in this model system thus seems to result exclusively from the activity of antiviral CD8 T cells, which recognize virus-infected cells in the brain. This view was recently confirmed by a study in which some features of the BDV-induced neurological disease were successfully recapitulated by adoptive transfer of virus-specific CD8 T cells into recipient mice that express viral antigen derived from a transgene that is active in either astrocytes or neurons.⁵Immune cell infiltrates are abundantly present in the brain of diseased wild-type MRL mice, but the infected organ usually shows no striking pathological alterations. However, in infected MRL mice lacking functional alleles of the IFN-γ gene, a selective and characteristic destruction of neurons was noted in the CA1 region of the hippocampus in about 50% of the mice.⁴ This destruction of neurons was paralleled by an influx of eosinophils, a cell type that is usually not found in the brain of BDV-infected wild-type mice.⁴ Interestingly, the CA1 neurons in these mice usually remain uninfected in mice.⁴The cause of the selective death of hippocampal neurons during BDV-induced brain inflammation in the absence of IFN-γ is not known. Several possible causes have been discussed, including excitotoxicity resulting from glutamate receptor overstimulation, as described for CA1 damage after measles virus,⁶ Sindbis virus^7,8 and HIV infection,⁹ and the possibility that the influx of eosinophils caused the neuronal damage possibly by secretion of toxic granule proteins, cytokines, or lipid mediators.¹⁰ Here we report that excitotoxicity and eosinophil influx are most likely not the cause of the observed CA1 neuron damage. Rather, our data suggest that the disease-inducing CD8 T cells play a decisive role. Interestingly, CA1 neuron damage was observed if CD8 T cells from IFN-γ-deficient but not from wild-type mice were adoptively transferred into uninfected mice that express transgene-encoded viral antigen selectively in astrocytes. These results suggest that the observed CA1 neuron death is a bystander phenomenon of T cell-mediated recognition of antigen-expressing astrocytes that only becomes evident if IFN-γ is absent.     

Linked Activity of Neurons in the Sensorimotor Cortex of the Rabbit in the State of a Defensive Dominant and “Animal Hypnosis”

A cryptic focus of excitation (a dominant focus) was created in the brains of rabbits by threshold stimulation of the left limb with a current at a frequency of 0.5 Hz. After creation of a focus, there were equal probabilities of detecting pairs of neurons whose linked activity was dominated by a 2-sec rhythm in the sensorimotor cortex of both the right and left hemispheres (29.3% and 32.4%, respectively). When animals were placed in “animal hypnosis,” the total proportion of neuron pairs whose activity was dominated by the rhythm created by establishment of the dominant decreased significantly only in the right hemisphere (21%). After exiting the state of animal hypnosis, the proportion of neurons in the cortex of the right hemisphere whose activity was dominated by the 2-sec rhythm increased significantly if the neurons in the pair were close-lying but decreased significantly if the neurons in the pair were mutually distant. No such changes after hypnotization were seen in the cortex of the left hemisphere. In both the right and left hemispheres, dominance of the 2-sec rhythm in the activity of pairs of neurons was seen significantly more frequently when cross-correlation histograms were constructed by analyzing cells in relation to the spike activity of neurons generating spikes of the lowest (right hemisphere) or lowest and intermediate (left hemisphere) amplitude on neurograms of multineuron activity. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 58, No. 2, pp. 183–193, March–April, 2008.     

An Optogenetic Study of the Electrophysiological Properties of Hippocampal Neurons in PS1-M146V Transgenic Mice (a model of Alzheimer’s disease)

Neuroscience and Behavioral Physiology - We report here a comparative (using chemical, electrical, and optical stimulation) study of the electrophysiological properties of cultured hippocampal...     

Studies of the Behavior of “Impulsive” and “Self-Controlled” Animals in an “Emotional Resonance” Test

Rats divided on the basis of a test in which they were presented with the “right” to choose a more valuable but delayed or a less valuable but immediate reinforcement into “impulsive” and “self-controlled” groups were studied using the “emotional resonance” method. These experiments showed that none of the rats of the “self-controlled” group, selecting the more valuable but delayed reinforcement, avoided defensive arousal signals from another individual of the same species, preferring to spend a large proportion of time in the dark “house.” Most (80%) of the animals of the “impulsive” group spent more than half the experimental period in the light sector, thus saving the partner from electrical stimulation. It is suggested that there are several common mechanisms underlying these two types of behavior.     

The Role of Neurons in the Orbitofrontal Cortex and Subthalamic Nucleus in Maintaining Intersignal Reactions in “Impulsive” and “Self-Controlled” Behavior

Neuroscience and Behavioral Physiology - Impulsivity is one of the most important symptoms of a whole series of mental disorders. Analysis of the activity of brain structures associated with the...     

Studies of Selective Attention in Dogs Using the Energy Characteristics of Neocortical Potentials in the Frequency Range 1–220 Hz

Experiments were performed in dogs to study the state of selective attention formed during operant food-related training and apparent during interstimulus intervals as a state of tense expectation of the conditioned signal. Electrical activity in various parts of the neocortex, in both hemispheres, was analyzed in the frequency range 1–220 Hz (epidural electrodes) using Fourier transforms. The electrical activity of the motor area of the right hemisphere showed a predominance of high-frequency (40–200 Hz) components, as did the visual and parietal areas of the left hemisphere. The state of selective attention was associated with a different functional mosaic in the organization of neocortical electrical activity.     

Donepezil Eliminates Suppressive Effects of β-Amyloid Peptide (1-42) on Long-Term Potentiation in the Hippocampus

β-Amyloid peptide 1-42 in a concentration of 200 nM impairs induction of long-term posttetanic potentiation of population spike in CA1 pyramidal neurons in rat hippocampal slices. Application of donepezil, a drug used for the treatment of Alzheimer disease, in a concentration of 1 μM eliminates the suppressive effect of β-amyloid peptide 1-42 on long-term posttenanic potentiation in the hippocampus.     

Acception of Cholesterol from Cells in Men of the Russian Population Correlates with Concentration of Pre-β1 High-Density Lipoproteins

We analyzed subfraction composition of HDL and cholesterol-acceptor properties of the plasma in Russian men with high and low HDL cholesterol. HDL were subfractionated by two-dimensional electrophoresis in agarose-polyacrylamide gel. The content of pre-beta1 HDL increased in individuals with high concentration of HDL cholesterol and strictly correlated with acception of cellular cholesterol in both groups.