Rabbit Neocortex Research Articles

Developmental Differences in Neocortex Neurogenesis and Maturation Between the Altricial Dwarf Rabbit and Precocial Guinea Pig.

Mammals are born on a precocial–altricial continuum. Altricial species produce helpless neonates with closed distant organs incapable of locomotion, whereas precocial species give birth to well-developed young that possess sophisticated sensory and locomotor capabilities. Previous studies suggest that distinct patterns of cortex development differ between precocial and altricial species. This study compares patterns of neocortex neurogenesis and maturation in the precocial guinea pig and altricial dwarf rabbit, both belonging to the taxon of Glires. We show that the principal order of neurodevelopmental events is preserved in the neocortex of both species. Moreover, we show that neurogenesis starts at a later postconceptional day and takes longer in absolute gestational days in the precocial than the altricial neocortex. Intriguingly, our data indicate that the dwarf rabbit neocortex contains a higher abundance of highly proliferative basal progenitors than the guinea pig, which might underlie its higher encephalization quotient, demonstrating that the amount of neuron production is determined by complex regulation of multiple factors. Furthermore, we show that the guinea pig neocortex exhibits a higher maturation status at birth, thus providing evidence for the notions that precocial species might have acquired the morphological machinery required to attain their high functional state at birth and that brain expansion in the precocial newborn is mainly due to prenatally initiating processes of gliogenesis and neuron differentiation instead of increased neurogenesis. Together, this study reveals important insights into the timing and cellular differences that regulate mammalian brain growth and maturation and provides a better understanding of the evolution of mammalian altriciality and presociality.

Neurovascular regulation is critical for metabolic recovery from spreading depression.

This scientific commentary refers to ‘Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma’ by Hinzman et al. (doi:10.1093/awu241). Long after Leao’s 1944 description of spreading depression in rabbit neocortex, scepticism remained over whether this phenomenon could be evoked or observed in the human brain (Somjen, 2001). Although many investigations have been carried out into the initiation, occurrence and spread of spreading depression, the mechanisms of ionic current flow underlying depolarization, and treatment paradigms (Pietrobon and Moskowitz, 2014), it is only recently that recording and imaging techniques have been able to confirm the occurrence of spreading depression in damaged human cortex, particularly in conditions involving trauma, subarachnoid haemorrhage, stroke, and possibly migraine headache with aura (Lauritzen et al. , 2011; Eikermann-Haerter et al. , 2012; Woitzik et al. , 2013). The intense depolarization and loss of ionic gradients in large volumes of brain tissue experiencing spreading depression means that significant substrate and metabolic capacity is required to generate energy for cell recovery (Somjen, 2001). If this metabolic need is unmatched by substrate supply (through neurovascular induction of increased blood flow), then propagation of brain damage can occur (Hossmann, 1994). In this issue of Brain , Hinzman and colleagues report a critical deficit in neurovascular coupling when spreading depression occurs near a traumatic brain lesion, in which decreased blood flow occurs in response to spreading depression (i.e. inverse neurovascular coupling) instead of increased blood flow, limiting the brain’s ability to meet the intense metabolic demand (Hinzman et al. , 2014). Although Hinzman and colleagues’ combined blood flow and electrocorticographic (ECoG) recording techniques only effectively worked in 5 of 24 patients, the spectrum of enhanced versus inverted neurovascular coupling in these five patients provides us with excellent examples of how proximity to a developing brain …

Activity of rabbit neocortex and hippocampus neurons in orientational-investigative behavior and freezing

Autocorrelation histograms were used to study the nature of spike activity in neurons recorded bilaterally from the visual and parietal areas of the cortex and hippocampal field CA1 in rabbits in free behavior during exposure to emotionally significant stimuli. Active movement orientational-investigative reactions to stimuli were associated with grouping of discharges and periodicity in the spike activity of most neurons in the cortex and hippocampus, this being dominated by the theta frequency (predominantly 4-5 Hz in the cortex and 4-5 and 6-7 Hz in the hippocampus). As compared with active movement reactions, freezing in response to stimulation was associated with increased numbers of neurons with uniform discharge distributions, while the spike activity of neurons with discharge periodicity showed increases in the intensity of the delta frequency (predominantly from 2 to 4 Hz), while theta intensity decreased. The number of neurons with periodic frequency in the delta range was greater in freezing than in the baseline state of calmly sitting rabbits.

Agonist Concentration-response Models in Mouse and Rabbit Neocortex: Re-evaluation of Classical Models in Comparison with a Recently Developed General Response Function

Agonist Concentration-response Models in Mouse and Rabbit Neocortex: Re-evaluation of Classical Models in Comparison with a Recently Developed General Response Function

Linked spike activity of rabbit neocortex neurons during self-stimulation of the lateral hypothalamus.

Cross-correlation and autocorrelation histograms were constructed to study the linkage between the spike activity of neurons in the visual and sensorimotor areas of both cerebral hemispheres in rabbits over periods of 10 sec after self-stimulation of the right and left lateral hypothalamus. Self-stimulation was followed by an increase in the number of pairs of cells in which neurons in the sensorimotor area fired after cells in the visual cortex (from 24 +/- 6% to 44 +/- 6%). Analysis of the spectrum of linked discharges revealed increases in the alpha and theta frequency ranges: the main increases in the right hemisphere were in the alpha range, while the main increases in the left hemisphere were in the theta range. Interhemisphere asymmetry in the interaction of cortical neurons was not associated with the side of the hypothalamus subjected to stimulation.

Relations between early prespike magnetic field changes, interictal discharges, and return to basal activity in the neocortex of rabbits

To evaluate possible prespike field synchronizations, its relation to both interictal discharges and postspike return to baseline, penicillin-induced cortical interictal discharges were recorded in anaesthetized rabbits by magnetoencephalography (MEG) and electrocorticography (EcoG). Statistical parameters of spatial (global field power (GFP)) and temporal properties (Z-parameter) of field synchronization were calculated. In our previous report, three types of prespike field synchronization were found before the onset of interictal spike. We report here that the continuous and fluctuating, but not the abrupt prespike increases, were more often associated with a spike and wave pattern of interictal discharge than with a spike alone. Furthermore, the postspike return of these statistical parameters shows the same three patterns as the prespike field synchronizations, but in the inverse time sequence. More often than not pre- and postspike pattern were of the same type. The results suggest an influence of prespike field synchronization upon interictal discharge and subsequent field return dynamics.

Effect of stimulation of the lateral hypothalamus on the correlation of neuron spike activity in the rabbit neocortex.

Cross-correlation and autocorrelation histograms were constructed with the aim of studying correlated spike activity of neurons in the visual and sensorimotor regions of both hemispheres of the rabbit brain before and after stimulation of the right and left lateral hypothalamic regions, which generates food-motivated responses. Stimulation of the left hypothalamus produced larger rearrangements in correlated neuron firing than stimulation of the right hypothalamus. Stimulation of the left hypothalamus, unlike that of the right hypothalamus, was followed by significant increases in the numbers of pairs of left hemisphere neocortical neurons with linked activity, and also induced the sequential firing of neurons in a particular defined order: sensorimotor cortex cells fired first, followed by visual cortex neurons after delays of up to 120 msec. It is concluded that cortical interhemisphere asymmetry in conditions of hunger is associated with nonuniform functioning of the right and left lateral hypothalamic regions.

Nonlinear analysis of epileptic activity in rabbit neocortex.

We report on the nonlinear analysis of electroencephalogram (EEG) recordings in the rabbit visual cortex. Epileptic seizures were induced by local penicillin application and triggered by visual stimulation. The analysis procedures for nonlinear signals have been developed over the past few years and applied primarily to physical systems. This is an early application to biological systems and the first to EEG data. We find that during epileptic activity, both global and local embedding dimensions are reduced with respect to nonepileptic activity. Interestingly, these values are very low (dE approximately equal to 3) and do not change between preictal and tonic stages of epileptic activity, also the Lyapunov dimension remains constant. However, between these two stages the manifestations of the local dynamics change quite drastically, as can be seen, e.g., from the shape of the attractors. Furthermore, the largest Lyapunov exponent is reduced by a factor of about two in the second stage and characterizes the difference in dynamics. Thus, the occurrence of clinical symptoms associated with the tonic seizure activity seems to be mainly related to the local dynamics of the nonlinear system. These results thus seem to give a strong indication that the dynamics remains much the same in these stages of behavior, and changes are due to alterations in model parameters and consequent bifurcations of the observed orbits.

Electrical activity of isolated rabbit cerebral cortex after direct application of acetylcholine.

Six weeks after surgical isolation of an extensive region of the rabbit neocortex, chronic experiments were carried out to study the EEG spectrum in baseline conditions and after macroapplication of acetylcholine (ACh) to the isolated cortex. Application of ACh elicited a complex, multiphasic response in the sensorimotor and visual regions of the isolated cortex, which lasted more than 10 min and consisted of an increase in the EEG amplitude with a gradual alteration in rhythmicity: there was an increase in theta activity, and higher-frequency (up to 15 Hz) processes appeared in the EEG trace. In control experiments (rabbits with intact cortex), application of ACh increased the EEG spectral amplitude and peak height. The response of the isolated cortex was interpreted as artificially induced activation, the level of activation determining the EEG spectrum. The differences in the responses of the isolated cortex and intact cortex result from preservation of control of the intact cortex by subcortical structures.

Influence of stimulation of the medial hypothalamus on the interaction of neurons of the rabbit neocortex.

The interaction of neurons of the visual and sensory motor areas of the neocortex of the rabbit before and after stimulation of some medial nuclei of the hypothalamus was investigated by plotting cross- and autocorrelation histograms. Stimulation through bipolar electrodes using bursts of biphasic pulses at a frequency of 100 Hz, current strength 50-200 microA, led to the appearance in freely behaving rabbits of the reaction of avoidance of the place of stimulation. Following stimulation, as compared with resting wakefulness, the number of pairs of neurons functioning in correlation increased to 45%; at the same time, discharges of neurons of the sensory motor area ran ahead of discharges of visual neurons in the pairs up to 120 msec; the periodicity of the coupled discharges was mainly in the theta frequency range. A conclusion regarding the reflection of defense motivation in certain indices of the interaction of the cortical cells in the presence of a tonic conditioned reflex is reached on the basis of a comparison of the interaction of neurons following stimulation of the medial hypothalamus and the midbrain reticular formation, in the intersignal periods during the development of a defense conditioned reflex as well.

5-HT 1D-like receptors inhibit the release of endogenously formed [ 3H]GABA in human, but not in rabbit, neocortex

Both human and rabbit brain contain the 5-hydroxytryptamine (5-HT) 1D subtype of 5-HT 1 receptors. We studied the effects of 5-HT 1D receptor stimulation on neocortical [ 3H]γ-aminobutyric acid (GABA) release from GABAergic neurons in these species. The 5-HT 1D receptor agonist sumatriptan depressed [ 3H]GABA release in human neocortex and the 5-HT 1 receptor antagonist metitepin prevented this depression with potencies suggesting mediation by 5-HT 1D-like receptors. In rabbit neocortex, however, 5-HT 1D agonists did not affect the release of [ 3H]GABA. Since 5-HT and GABA seem to function antagonistically in anxiety disorders their neocortical interaction may be (patho)physiologically relevant.

The influence of high-frequency stimulation of the midbrain reticular formation on the interaction of neurons of the neocortex.

The influence of the stimulation of the midbrain reticular formation (NRT) at a frequency of 75-100 Hz, current strength 33-400 microA, on the interaction of neurons of the visual and sensorimotor areas of the neocortex of rabbits was investigated. Cross- and autocorrelation histograms of the impulse sequences were plotted. Stimulation of the NRT led to an increase in the number of pairs of neurons functioning in correlation and an increase in the probability of discharges of neurons one after the other with delays from 100 to 400 msec as compared with resting wakefulness. The mechanisms of the interaction of the cells were not altered in the process. Comparison with previously obtained data made it possible to conclude that activation of the NRT may lead to specific changes in the interaction of neurons which are observable during pseudoconditioning and at the beginning of the development of a conditioned reflex.

A Note on the Action of Glutamine on Cortical Spreading Depression

Application of a solution of 1-glutamine, 75 mM, to the pia-arachnoid surface of the dorsolateral neocortex of rabbits under dial-urethane anaesthesia was found to reversibly render the tissue insusceptible to spreading depression. It is suggested that this amide may play a part in the opposition normally offered by the tissue to undergo spreading depression. Some evidence is adduced which seems to support this suggestion.

Studies on substances that induce long-term potentiation in guinea-pig hippocampal slices

Fluids were collected from the rabbit neocortex during a tetanic stimulation of the cortical surface. When these samples from the neocortex were applied on the guinea-pig hippocampal slices, only those fractions containing substances with molecular weights <3000, 3000–10,000and> 50,000 and not with other molecular weights, could induce long-term potentiation of population spikes in the CA1 area in response to stratum radiatum stimulation. Intracellular recordings from the CA1 neurons revealed that the long-term potentiation-inducing substances increased the excitatory postsynaptic potential without changing the membrane potential and the input resistance of these cells. A pretreatment of the rabbits with MK-801 prevented the release of the long-term potentiation-inducing substances. 2-Amino-5-phosphonovalerate was unable to block the long-term potentiation-inducing action of the substances from the rabbit neocortex. Gel-electrophoresis of the substances collected from the rabbit neocortex revealed the presence of an acidic peptide with a molecular weight of about 69,000. These results indicate that tetanic stimulatio of rabbit neocortex results in a release of substances with molecular weights of <3000, 3000–10,000and> 50,000 that could induce long-term potentiation in guinea-pig hippocampal slices. The release, but not the long-term potentiation-inducing action, of these substances appears to depend on the activation of N-methyl- d-aspartate receptors. The long-term potentiation-inducing substance in the 50,000mol. wt fraction may be an acidic peptide with a molecular weight of about 69,000.

Comparison of coupling of impulse activity of cerebral cortical neurons and spatial synchronicity of the EEG

The coherence of the EEG and the coupling of the impulse activity of neurons of the visual and sensorimotor areas of the neocortex of rabbits, recorded simultaneously from the same electrodes, were compared under chronic experimental conditions. An association was found between the presence and properties of the conjugated functioning of neurons and the coherence of the EEG at various frequencies. Greater coherence of the EEG was observed during the correlated functioning of neurons at frequencies of 3-4.5 Hz than during independent functioning. The neurons discharged in pairs, with a smaller delay between them at the highest level of EEG coherence, and a common source participating more often in their synchronization than at the lowest level of EEG coherence.

The influence of an enkephalin derivative, DAGO, on the behavior and activity of neurons of the neocortex and hippocampus of rabbits during the development of defensive and inhibitory conditioned reflexes

After the administration of a morphine-like opiate, DAGO (D), in a dose of 250 micrograms/kg, a decrease was observed in the probability of movements of a rabbit in response to light flashes, the signal for a defensive reflex. The level of the background impulse activity of the neurons gradually decreased in the sensorimotor cortex and in the hippocampus, and did not change in the visual cortex. The decrease and the recovery of the responses of the neurons to the reinforcing stimulus (electrodermal stimulation of the limb) proceeded unidirectionally in all of the areas of the cortex studied, while there were substantial differences in the relationship to the cortical area studied and to the biological significance of the stimulus in the dynamics of the responses to the inhibitory and reinforced light flashes. The identification of the features of the systemic organization of the neurons during training with change in the properties of the reinforcement under the influence of the preparation under study is discussed, as well as the similarity of some features in the mechanisms of the development of internal inhibition in the defensive situation and of the properties of positive reinforcement.

Influence of piracetam on activity of neurons of the neocortex of rabbits during learning.

1. Against the background of the action of piracetam, a cyclic derivative of GABA in a dose of 200–400 mg/kg, significant changes were not observed in the probabilities of motor reactions of awake rabbits to light flases, reinforced by electrocutaneous stimulation of the extremity, and to flashes switched on against the background of a conditional inhibitor without reinforcement. 2. Piracetam in the dose employed did not affect the inhibitory pauses in the reactions of neurons of the visual area, and the late components corresponding to them of the potential evoked in response to non-reinforced light flashes, i.e., did not intensify the inhibitory hyperpolarizational processes in the cerebral cortex. 3. Following the administration of piracetam, the differentiation of inhibitory and reinforced light flashes improved, according to bioelectrical indices of the operation of the brain, as the result of the intensification of the effect of painful reinforcement on the neurons of the cortex. 4. These experiments revealed substantial differences in the neurophysiological mechanisms of action of piracetam and fenibut, a linear derivative of GABA, which are classified as nootropic agents.

Substances released during tetanic stimulation of rabbit neocortex induce neurite growth in PC-12 cells and long-term potentiation in guinea pig hippocampus

Samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex induced neurite growth in PC-12 cells in culture and synaptic long-term potentiation (LTP) in guinea pig hippocampal slices. If these samples were preheated and cooled, or if they were collected in the absence of a tetanic stimulation of the rabbit neocortex, they did not induce neurite growth in PC-12 cells or LTP in the guinea pig hippocampus. These results suggest that neurite-inducing factors are released during tetanic stimulations and that these substances are involved in LTP.

Duration of trace processes in rabbit neocortex.

1. Using nonimmobilized and nonanesthetized rabbits we have demonstrated prolonged (1 h of more) posttetanic changes in the response of the pyramidal tract (PT) following brief tetanization, close to natural stimulation conditions. 2. The analysis of the changes in the PT response revealed a prolonged potentiation of monosynatic neocortical reactions characterized by low frequency depression and self-restoration 3. Data on the predominant, more marked and prolonged increase in the synaptic component of the PT response indicate that the increase in the efficiency of the excitatory synaptic connections represents the main mechanism of prolonged potentiation. 4. The data obtained on the less prolonged and unstable nature of changes in the D component suggest that a change in the excitability of nerve cells could be only a supplementary mechanism of prolonged potentiation.

Conjugation of unit activity in the visual and sensorimotor areas of rabbit neocortex during conditioned reflexes to light and sound.

1. The number of pairs of neurons of the visual and sensorimotor regions of the neocortex functioning in correlation during the intersignal intervals in groups of rabbits with CRs to light and CRs to sound show no differences. 2. The distribution of cross-correlation histograms with respect to their shapes show no differences in the groups analyzed; this indicates a similarity of basic mechanisms caused by correlated discharges. 3. The delays in the discharges of neurons of one region after another differ in the two groups of rabbits. In the rabbits with a CR to light, there is a predominance of the number of neurons of the visual region discharging with a delay of 125 msec after the neurons of the sensorimotor region over the number of neurons of the sensorimotor region discharging after the neurons of the visual region. In rabbits with a CR to sound, the number of neurons of the visual region with such a delay in discharges after the discharges of the sensorimotor region were fewer, and a predominance of the number of neurons of the sensorimotor region discharging after discharges of the visual region could even be detected 30–60 sec after the stimuli. 4. In certain fragments, several predominant delays in the discharges of one neuron after another were detected in both the 1st and the 2nd groups. 5. The results obtained indicate that there is no specificity in the tendency of neurons of the visual and sensorimotor regions of the cortex to join in conjugated operation in cases when both of these regions, or only one of them, are representations of conditioned and unconditioned stimuli. At the same time, qualitative differences in the conjugated functioning of neurons exist; these concern the start-up order of cells in pairs.