Analysis of the reactivity of the sensorimotor neurons of the rat cerebral cortex to acetylcholine

Several types of cholinoceptive neurons have been identified in rat's sensomotor cortex according to response character to ionophoretical application of acetylcholine. The neurons investigated form continuous range according to duration of the excitatory component of reaction to transmitter application. It has been suggested that the duration of this component reflects the important functional properties of the nerve cell.     

Analysis of the form of cortical neuron reaction to acetylcholine

Reaction patterns of 90 cortical neurons to acetylcholine approximated by two parabolas have been divided on simple and complex. The participation of different types of cholinoreceptors in complex reactions to transmitter is proposed.     

Plasticity and its physiological markers in the microsystem of cortical neurons during repeated local stimulation

Separate neuronal microsystems in the sensomotor cerebral cortex are able to exhibit the functional plasticity under conditions of repeated action of acetylcholine applied microiontophoretically. The characteristic properties of dynamics in activity of single cortex neurones are determined mainly by the initial reactivity to transmitter and by the state of nervous cells of the surrounding microsystem. The composition and succession of response components as well the duration of excitatory stage of reaction to acetylcholine serve as physiological markers of plastic properties of neurones in cortical microsystem.     

猫初级视皮层内GIu/GABA表达比率的衰老性变化

最近的一些研究结果显示,视皮层内抑制性递质系统作用减弱可能是导致老年性视觉功能衰退的重要因素.是否皮层内兴奋性递质系统亦伴随衰老而发牛改变并影响皮层内神经兴奋与抑制的平衡尚不清楚.为此,利用Nissl染色和免疫组织化学染色方法以及Image-Pro Express图像分析软件对青、老年猫初级视皮层(17区)内各层神经元密度、兴奋性递质谷氨酸免疫反应阳性(Glu-immunoreactive,Glu-IR)神经元密度以及抑制性递质γ-氨基丁酸免疫反应阳性(γ-aminobutyric acid.immunoreactive,GABA-IR)神经元密度进行了统汁分析.结果显示,青、老年猫初级视皮层各层神经元密度均没有明显的年龄性差异(P>0.05);与青年猫相比,老年猫初级视皮层Glu-IR、GABA-IR神经元密度均显著减少(P<0.01),而Glu.IR/GABA.IR神经元密度比率去却显著增大(P<0.01).结果提示,老年猫初级视皮层内兴奋性递质系统作用相对增强,而抑制性递质系统的作用相对减弱,导致皮层内兴奋-抑制平衡关系失调,这可能是引起老年个体视觉功能衰退的重要原因之一.     

Interactions of glutamate and dopamine in a computational model of the striatum

A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.     

Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways

Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons.     

Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex.

Adenosine and the adenine nucleotides have a potent depressant action on cerebral cortical neurons, including identified corticospinal cells. Other purine and pyrimidine nucleotides were either weakly depressant (inosine and guanosine derivatives) or largely inactive (xanthine, cytidine, thymidine, uridine derivatives). The 5'-triphosphates and to a lesser extent the 5'-diphosphates of all the purine and pyrimidines tested had excitant actions on cortical neurons. Adenosine transport blockers and deaminase inhibitors depressed the firing of cortical neurons and potentiated the depressant actions of adenosine and the adenine nucleotides. Methylxanthines (theophylline, caffeine, and isobutylmethylxanthine) antagonized the depressant effects of adenosine and the adenine nucleotides and enhanced the spontaneous firing rate of cerebral cortical neurons. Intracellular recordings showed that adenosine 5'-monophosphate hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials in the absence of any pronounced alterations in membrane resistance or of the threshold for action potential generation. It is suggested that adenosine depresses spontaneous and evoked activity by inhibiting the release of transmitter from presynaptic nerve terminals. Furthermore, the depressant effects of potentiators and excitant effects of antagonists of adenosine on neuronal firing are consistent with the hypothesis that cortical neurons are subject to control by endogenously released purines.     

The maturation of the somatostatin systems in the rat visual cortex

The development of somatostatin-immunoreactive (SS) neurons and processes in the rat visual cortex (VC) was studied in animals from embryonic day 20 (E20) to postnatal day 21 (D21). Three distinct patterns of immunoreactivity were seen. From E20 to birth (D0), VC was characterized by a small number of mainly bipolar SS neurons throughout the cortical plate. In the perinatal period, from D1 to D6, there were large numbers of immature immunoreactive neurons which were confined to layer VI and the subplate zone, a few bipolar neurons in the cortical plate and an extremely dense plexus of SS processes throughout the neuropil. The third phase, from D8 to weaning, was characterized by the absence of immature SS neurons, an increase in the number of multipolar SS neurons and a decrease in the density of SS fibers. By D15, the time of eye-opening, the number and distribution of SS neurons and processes was close to that seen in the adult. These results indicate that the SS system of neurons and fibers is among the earliest of the transmitter systems to be established in VC and suggests a role for the peptide in cortical organization as well as visual processing.     

Modification of chemoreactive properties of neurons in the neocortex and hippocampus under the effect of electric stimulation of locus coeruleus

Based on the findings of alterations in the chemoreactivity of neurons under conditioning and its possible significance for the formation of transient neuronal junctions, the authors investigated the influence of electrical stimulation of the Locus coeruleus upon the transmitter sensitivity of cortical and hippocampal neurons. The majority of neurons showed immediately after stimulation of the Locus coeruleus a different reaction to microiontophoretic application of acetylcholine, dopamine and glutamate than under normal conditions. Obviously there must have occurred qualitative changes because a superposition effect of the reactions following stimulation of the Locus coeruleus and application of the substances has rarely been observed. The release of noradrenaline provoked by the stimulation of the Locus coeruleus evidently leads to qualitative changes in the neurone texture, which may occur both inter- and intraneuronally.     

An analysis of the transitions between down and up states of the cortical slow oscillation under urethane anaesthesia

We study the dynamics of the transition between the low- and high-firing states of the cortical slow oscillation by using intracellular recordings of the membrane potential from cortical neurons of rats. We investigate the evidence for a bistability in assemblies of cortical neurons playing a major role in the maintenance of this oscillation. We show that the trajectory of a typical transition takes an approximately exponential form, equivalent to the response of a resistor–capacitor circuit to a step-change in input. The time constant for the transition is negatively correlated with the membrane potential of the low-firing state, and values are broadly equivalent to neural time constants measured elsewhere. Overall, the results do not strongly support the hypothesis of a bistability in cortical neurons; rather, they suggest the cortical manifestation of the oscillation is a result of a step-change in input to the cortical neurons. Since there is evidence from previous work that a phase transition exists, we speculate that the step-change may be a result of a bistability within other brain areas, such as the thalamus, or a bistability among only a small subset of cortical neurons, or as a result of more complicated brain dynamics.     

Excitability changes of cortical neurons during the postnatal period in rats exposed to prenatal hypobaric hypoxia

Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed.     

Alpha- and beta-oscillations of dynamics of the area and weight of receptive fields of cat striate neurons under conditions of classical and combined mapping

In 22 acute experiments in anesthetized and immobilized adult cats the dynamics of 83 receptive fields (RF) of 47 striate neurons was studied by temporal slices method. Classical mapping revealed wave-like changes in the area and weight of neuronal RFs. Special mathematical analysis showed that such changes represented a sum of a slow non-oscillatory and comparatively fast components. The slow component was a biphasic up and down RF dynamics. In most cases, the oscillation frequencies were within the alpha- and beta- EEG frequency ranges. When the RF center was activated additionally during combined mapping, the oscillations frequencies remained unchanged, but the duration and amplitude of non-oscillatory component substantially decreased. Mechanisms underlying the RF dynamics and its functional significance are discussed.     

Aspartate Aminotransferase Activity in Fiber Tracts of the Rat Brain

Activity of aspartate aminotransferase, an enzyme which catalyzes the interconversion of the excitatory transmitter candidates, glutamate and aspartate, has been measured in fiber tracts of rat, with an emphasis on sensory and motor systems of the brain. Most tracts had significantly higher activities than the cholinergic facial nerve root, consistent with the possibility that a component of aspartate aminotransferase activity might serve as a marker for neurons using glutamate and/or aspartate as neurotransmitter. Highest activity was in the auditory nerve root. On the other hand, a close correlation was found between aspartate aminotransferase and malate dehydrogenase activities in the fiber tracts, raising the question whether aspartate aminotransferase activity may be more closely related to energy metabolism than to transmitter metabolism.     

Exploring the spectrum of dynamical regimes and timescales in spontaneous cortical activity

Rhythms at slow (<1 Hz) frequency of alternating Up and Down states occur during slow-wave sleep states, under deep anaesthesia and in cortical slices of mammals maintained in vitro. Such spontaneous oscillations result from the interplay between network reverberations nonlinearly sustained by a strong synaptic coupling and a fatigue mechanism inhibiting the neurons firing in an activity-dependent manner. Varying pharmacologically the excitability level of brain slices we exploit the network dynamics underlying slow rhythms, uncovering an intrinsic anticorrelation between Up and Down state durations. Besides, a non-monotonic change of Down state duration is also observed, which shrinks the distribution of the accessible frequencies of the slow rhythms. Attractor dynamics with activity-dependent self-inhibition predicts a similar trend even when the system excitability is reduced, because of a stability loss of Up and Down states. Hence, such cortical rhythms tend to display a maximal size of the distribution of Up/Down frequencies, envisaging the location of the system dynamics on a critical boundary of the parameter space. This would be an optimal solution for the system in order to display a wide spectrum of dynamical regimes and timescales.     

Cortical songs revisited: a lesson in statistics

Recordings from single neurons in the cortex have revealed precisely repeating patterns of synaptic events. These repeats are known as cortical "motifs" and have been suggested to reflect the precise replay of spatiotemporal firing sequences ("synfire" chains). In this issue of Neuron, Mokeichev et al. use compelling statistical analysis to show that, rather than being evidence of deterministic synfire chains, such cortical motifs are bound to appear by chance due to the natural dynamics of voltage fluctuations in neurons.     

Neuronal and synaptic mechanisms of cortical inhibition

The latent periods, amplitude, and duration of IPSPs arising in neurons in different parts of the cat cortex in response to afferent stimuli, stimulation of thalamocortical fibers, and intracortical microstimulation are described. The duration of IPSPs evoked in cortical neurons in response to single afferent stimuli varied from 20 to 250 msec (most common frequency 30–60 msec). During intracortical microstimulation of the auditory cortex, IPSPs with a duration of 5–10 msec also appeared. Barbiturates and chloralose increased the duration of the IPSPs to 300–500 msec. The latent period of 73% of IPSPs arising in auditory cortical neurons in response to stimulation of thalamocortical fibers was 1.2 msec longer than the latent period of monosynaptic EPSPs evoked in the same way. It is concluded from these data that inhibition arising in most neurons of cortical projection areas as a result of the arrival of corresponding afferent impulsation is direct afferent inhibition involving the participation of cortical inhibitory interneurons. A mechanism of recurrent inhibition takes part in the development of inhibition in a certain proportion of neurons. IPSPs arise monosynaptically in 2% of cells. A study of responses of cortical neurons to intracortical microstimulation showed that synaptic delay of IPSPs in these cells is 0.3–0.4 msec. The length of axons of inhibitory neurons in layer IV of the auditory cortex reaches 1.5 mm. The velocity of spread of excitation along these axons is 1.6–2.8 msec (mean 2.2 msec).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 394–403, May–June, 1984.     

Synthesis and release of GABA in cerebral cortical neurons co-cultured with astrocytes from cerebral cortex or cerebellum

Cerebral cortical neurons were co-cultured for up to 7 days with astrocytes after plating on top of a confluent layer of astrocytes cultured from either cerebral cortex or cerebellum (sandwich co-cultures). Neurons co-cultured with either cortical or cerebellar astrocytes showed a high stimulus coupled release of gamma-aminobutyric acid (GABA), which is the neurotransmitter of these neurons. When the astrocyte selective GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol was added during the release experiments, an increase in the stimulus coupled GABA release was seen, indicating that the astrocytes take up a large fraction of GABA released from the neurons. The activity of the GABA synthesizing enzyme glutamate decarboxylase, which is a specific marker of GABAergic neurons, was markedly increased in sandwich co-cultures of cortical neurons and cerebellar astrocytes compared to neurons cultured in the absence of astrocytes whereas in co-cultures with cortical astrocytes this increase was less pronounced. Pure astrocyte cultures did not show any detectable glutamate decarboxylase activity. The astrocyte specific marker enzyme glutamine synthetase (GS) was present at high activity in a glucocorticoid-inducible form in pure astrocytes as well as in co-cultures regardless of the regional origin of the astrocytes. When neurons were cultured on top of the astrocytes, the specific activity of GS was lower compared to astrocytes cultured alone, a result compatible with the notion that neurons are devoid of this enzyme. The results show that cortical neurons develop and differentiate when seeded on top of both homotypic and heterotypic astrocytes. Moreover, it could be demonstrated that the two cell types in the culture system communicate with each other with regard to GABA homeostasis during transmitter release.     

The effect of acetylcholine on shifts in the spatial synchronization of the cortical potentials in the rabbit evoked by the reversible interruption of the mammillary body connections

To study the role of cholinergic transmitter system in the maintenance of sychronizing limbic influences, the dynamics of the spatial distribution of the changes of cross-correlation coefficients of rabbits EEG led by 24 electrodes, was estimated at application of acetylcholine solution to the visual cortical area in combination with anode polarization of mammillary bodies. Acetylcholine, which separate effect was connected with a restricted increase of the spatial synchronization of potentials, completely eliminated the effects of isolated polarization expressed in a significant decrease of a half of calculated correlation coefficients between EEGs of the visual and motor cortical areas. Nonspecific cholinergic synchronizing system is supposed to exist which is active under the conditions of the mammillo-thalamo-cortical connections being intact.     

Activity dynamics and propagation of synchronous spiking in locally connected random networks

Random network models have been a popular tool for investigating cortical network dynamics. On the scale of roughly a cubic millimeter of cortex, containing about 100,000 neurons, cortical anatomy suggests a more realistic architecture. In this locally connected random network, the connection probability decreases in a Gaussian fashion with the distance between neurons. Here we present three main results from a simulation study of the activity dynamics in such networks. First, for a broad range of parameters these dynamics exhibit a stationary state of asynchronous network activity with irregular single-neuron spiking. This state can be used as a realistic model of ongoing network activity. Parametric dependence of this state and the nature of the network dynamics in other regimes are described. Second, a synchronous excitatory stimulus to a fraction of the neurons results in a strong activity response that easily dominates the network dynamics. And third, due to that activity response an embedding of a divergent-convergent feed-forward subnetwork (as in synfire chains) does not naturally lead to a stable propagation of synchronous activity in the subnetwork; this is in contrast to our earlier findings in isolated subnetworks of that type. Possible mechanisms for stabilizing the interplay of volleys of synchronous spikes and network dynamics by specific learning rules or generalizations of the subnetworks are discussed.     

Ultrastructure of sensorimotor cortex neurons in the progeny of rats receiving alcohol during pregnancy

Dynamics of ultrastructural changes in the sensomotor cortex neurons has been studied on the 21st, 30th and 60th days of life in offspring born by the rats given 20% alcohol (2 g/kg) during pregnancy. Moderate antenatal alcoholization produces certain disturbances in the ultrastructure of the cortical neurons and their dendrites. This is manifested as presence of retardation signs in maturation of nervous cell populations, as dystrophic changes in the neurons and their dendrites and display of reparative character with their own dynamics in the postnatal period of ontogenesis. The first two categories of the ultrastructural changes in the cortical neurons are more manifested at early stages of the postnatal development of the offspring, and the reparative processes--at the age of two months. Despite the presence of the reparative shifts, the dystrophic changes of the neurons of hypoxic character are present up to the period of sexual maturation. This demonstrates that the antenatal alcoholic intoxication in the offspring is manifested in the postnatal ontogenesis for a long time.