Cortical Neuronal Networks Research Articles

Evidence for homeostatic adjustments of rat somatosensory cortical neurons to changes in extracellular acetylcholine concentrations produced by iontophoretic administration of acetylcholine and by systemic diisopropylfluorophosphate treatment

We describe the responses of single units in the awake (24 cells) or urethane-anesthetized (37 cells) rat somatosensory cortex during repeated iontophoretic pulses (1.0 s, 85 nA) of acetylcholine, both before and after systemic treatment with the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (i.p., 0.3–0.5 ld 50). The time-course of the response to acetylcholine pulses differed among cortical neurons but was characteristic for a given cell. Different time-courses included monophasic excitatory or inhibitory responses, biphasic (excitatory–inhibitory, inhibitory–excitatory, excitatory–excitatory, and inhibitory–inhibitory), and triphasic (excitatory–excitatory–inhibitory, inhibitory–inhibitory–excitatory, and inhibitory–excitatory–inhibitory) responses. Although the sign and time-course of the individual responses remained consistent, their magnitude fluctuated across time; most cells exhibited either an initial increase or decrease in response magnitude followed by oscillations in magnitude that diminished with time, gradually approaching the original size. The time-course of the characteristic response to an acetylcholine pulse appeared to determine direction and rate of change in response magnitude with successive pulses of acetylcholine. Diisopropylfluorophosphate treatment, given 1 h after beginning repeated acetylcholine pulses, often resulted in a gradual increase in spontaneous activity to a slightly higher but stable level. Superimposed on this change in background activity, the oscillations in the response amplitude reappeared and then subsided in a pattern similar to the decay seen prior to diisopropylfluorophosphate treatment. Our results suggest that dynamic, homeostatic mechanisms control neuronal excitability by adjusting the balance between excitatory and inhibitory influences within the cortical circuitry and that these mechanisms are engaged by prolonged increases in extracellular acetylcholine levels caused by repeated pulses of acetylcholine and by acetylcholinesterase inhibition. However, this ability of neurons in the cortical neuronal network to rapidly adjust to changes in extracellular levels of acetylcholine questions the potential efficacy of therapeutic treatments designed to increase ambient levels of acetylcholine as a treatment for Alzheimer's disease or to enhance mechanisms of learning and memory.

Simultaneous Induction of Pathway-Specific Potentiation and Depression in Networks of Cortical Neurons

Activity-dependent modification of synaptic efficacy is widely recognized as a cellular basis of learning, memory, and developmental plasticity. Little is known, however, of the consequences of such modification on network activity. Using electrode arrays, we examined how a single, localized tetanic stimulus affects the firing of up to 72 neurons recorded simultaneously in cultured networks of cortical neurons, in response to activation through 64 different test stimulus pathways. The same tetanus produced potentiated transmission in some stimulus pathways and depressed transmission in others. Unexpectedly, responses were homogeneous: for any one stimulus pathway, neuronal responses were either all enhanced or all depressed. Cross-correlation of responses with the responses elicited through the tetanized site revealed that both enhanced and depressed responses followed a common principle: activity that was closely correlated before tetanus with spikes elicited through the tetanized pathway was enhanced, whereas activity outside a 40-ms time window of correlation to tetanic pathway spikes was depressed. Response homogeneity could result from pathway-specific recurrently excitatory circuits, whose gain is increased or decreased by the tetanus, according to its cross-correlation with the tetanized pathway response. The results show how spatial responses following localized tetanic stimuli, although complex, can be accounted for by a simple rule for activity-dependent modification.

Analysis of a correlation-based model for the development of orientation-selective receptive fields in the visual cortex

We analyse a model for the development of orientation-selective receptive fields of simple cells in a locally connected network of cortical neurons. The Hebbian learning rule that underlies the development is described by a linear differential equation. The structure of the emerging cortical map can be predicted by deriving the eigenfunctions corresponding to the leading eigenvalues of the associated matrix. We show that the receptive fields have the typical form of a wavelet. Mathematically, receptive fields are given by a Hermitian polynomial with Gaussian cut-off and a phase factor. Both the phase of the wavelet and the orientation are changing periodically along the surface of the cortical map as suggested by previous simulation studies and as also found in experiments. In order to get orientation-selective receptive fields, the spatial correlation function of the inputs that drive the development must have a zero crossing.

Background gamma-oscillations in neuronal networks with interhemisphere connections.

Results obtained in studies of the high-frequency components of EEG recordings and in modeling, determining the conditions for the appearance of gamma oscillations in interneuronal interactions, were compared with features of the background gamma oscillations recorded in the activity of interacting neurons located in symmetrical loci of the right and left hemisphere motor areas in anesthetized rats. Similarities in high frequencies extracted from EEG recordings and in the most commonly observed gamma oscillation frequencies suggested that these oscillations may represent one of the mechanisms underlying the high-frequency EEG component. Published modeling data indicating that the formation of these oscillations involves reciprocal inhibitory connections, along with our own data that interhemisphere oscillations are seen 1.5 times more commonly than ipsilateral oscillations, suggested that transcallosal inhibition is more effective than inhibition between neighboring cells. Simultaneously extracted background oscillations in the interacting activity of callosal cells and neighboring cells could be different, as could those characterizing the activity of individual neurons. It is suggested that these differences underlie the functional heterogeneity of local cortical neuronal networks and explain the fact that these networks contain various types of inhibitory neurons.

Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons.

In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2-3 Hz and fast runs at 10-15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. We performed single and dual simultaneous intracellular recordings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both components of seizures were analyzed, but emphasis was placed on the fast runs because of their recent investigation at the cellular level. 1) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, dorsal thalamic nuclei, although receiving convergent inputs from different neocortical areas involved in seizure, did not express strongly synchronized fast runs. 2) Both RE and TC cells were hyperpolarized during seizure episodes with SW/PSW complexes and relatively depolarized during the fast runs. As known, hyperpolarization of thalamic neurons deinactivates a low-threshold conductance that generates high-frequency spike bursts. Accordingly, RE neurons discharged prolonged high-frequency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials, spike doublets, or triplets during the fast runs. In TC cells, the cortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynaptic activation through corticothalamic pathways. 3) The above data suggested the cortical origin of these seizures. To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.

Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus.

We explored the relative contributions of cortical and thalamic neuronal networks in the generation of electrical seizures that include spike-wave (SW) and polyspike-wave (PSW) complexes. Seizures were induced by systemic or local cortical injections of bicuculline, a gamma-aminobutyric acid-A (GABAA) antagonist, in cats under barbiturate anesthesia. Field potentials and extracellular neuronal discharges were recorded through arrays of eight tungsten electrodes (0.4 or 1 mm apart) placed over the cortical suprasylvian gyrus and within the thalamus. 1) Systemic injections of bicuculline induced SW/PSW seizures in cortex, whereas spindle sequences continued to be present in the thalamus. 2) Cortical suprasylvian injection of bicuculline induced focal paroxysmal single spikes that developed into full-blown seizures throughout the suprasylvian cortex. The seizures were characterized by highly synchronized SW or PSW complexes at 2-4 Hz, interspersed with runs of fast (10-15 Hz) activity. The intracellular aspects of this complex pattern in different types of neocortical neurons are described in the following paper. Complete decortication abolished the seizure, leaving intact thalamic spindles. Injections of bicuculline in the cortex of athalamic cats resulted in similar components as those occurring with an intact thalamus. 3) Injection of bicuculline in the thalamus decreased the frequency of barbiturate spindles and increased the synchrony of spike bursts fired by thalamocortical and thalamic reticular cells but did not induce seizures. Decortication did not modify the effects of bicuculline injection in the thalamus. Our results indicate that the minimal substrate that is necessary for the production of seizures consisting of SW/PSW complexes and runs of fast activity is the neocortex.

Cellular dynamics of network memory.

One example of "emergence" is the development, as a result of neural ontogeny and living experience, of cortical networks capable of representing and retaining cognitive information. A large body of evidence from neuropsychology, electrophysiology and neuroimaging indicates that so-called working memory and long-term memory share the same neural substrate in the cerebral cortex. That substrate consists in a system of widespread, overlapping and hierarchically organized networks of cortical neurons. In this system, any neuron or group of neurons can be part of many networks, and thus many memories. Working memory is the temporary activation of one such network of long-term memory for the purpose of executing an action in the near future. The activation of the network may be brought about by stimuli that by virtue of prior experience are in some manner associated with the cognitive content of the network, including the response of the organism to those stimuli. The mechanisms by which the network stays activated are presumed to include the recurrent re-entry of impulses through associated neuronal assemblies of the network. Consistent with this notion is the following evidence: (1) working memory depends on the functional integrity of cortico-cortical connective loops; and (2) during working memory, remarkable similarities--including "attractor behavior"--have been observed between firing patterns in real cortex and in an artificial recurrent network.

Effects of α-pompilidotoxin on synchronized firing in networks of rat cortical neurons

We studied the effect of a novel neurotoxin, α-pompilidotoxin ( α-PMTX) on the spontaneously synchronized network firing of cultured rat cortical neurons. α-PMTX acted immediately and irreversibly to disrupt synchronous activity, leaving only residual sparse, uncorrelated firing and was effective at concentrations of 10 nM. In the presence of bicuculline to block inhibitory synaptic transmission, the shutdown in synchronized activity occurred with a significant delay, required a higher concentration of α-PMTX (>100 nM), and was preceded by a transiently increased level of firing. It appears that both inhibitory and excitatory neuronal activity or synaptic transmission are amplified by α-PMTX, but that intense activity eventually leads to inactivation or transmitter depletion.

Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30-40 Hz) spike bursts.

Fast spontaneous oscillations (mainly 30-40 Hz) characterize cortical and thalamic neuronal networks during behavioral states of increased vigilance and depend on cell depolarization under the influence of ascending activating systems. We investigated, by means of intracellular recording and staining in vivo, the properties of fast-oscillating cortical neurons from cat's motor and association areas, some projecting to the thalamus, others with locally arborizing axons. At a given level of depolarization, 28% of our neuronal sample discharged high-frequency spike bursts (300-600 Hz) that recurred rhythmically between 20 and 50 Hz. Such fast rhythmic bursting neurons have been found in both superficial and deep cortical layers. Slight changes in membrane potential as well as synaptic activity in thalamocortical networks dramatically altered the discharge patterns, from single spikes to rhythmic spike-bursts, and eventually to fast tonic firing without frequency adaptation. Thus our data challenge the conventional idea that sharply defined, invariant features and distinct locations in certain cortical layers characterize some neocortical cell-classes. We demonstrate that the distinctions between intrinsic electrophysiological properties of neocortical neurons are much more labile than conventionally thought. The present results, which indicate that corticothalamic neurons discharge fast rhythmic spike bursts mainly at 30-40 Hz, suggest that this activity results in integrated fast oscillations within corticothalamic networks.

Analysis of a correlation-based model for the development of orientation-selective receptive fields in the visual cortex

We analyse a model for the development of orientation-selective receptive fields of simple cells in a locally connected network of cortical neurons. The Hebbian learning rule that underlies the development is described by a linear differential equation. The structure of the emerging cortical map can be predicted by deriving the eigenfunctions corresponding to the leading eigenvalues of the associated matrix. We show that the receptive fields have the typical form of a wavelet. Mathematically, receptive fields are given by a Hermitian polynomial with Gaussian cut-off and a phase factor. Both the phase of the wavelet and the orientation are changing periodically along the surface of the cortical map as suggested by previous simulation studies and as also found in experiments. In order to get orientation-selective receptive fields, the spatial correlation function of the inputs that drive the development must have a zero crossing.

Experimental analysis of neuronal dynamics in cultured cortical networks and transitions between different patterns of activity

Experimental investigation of the dynamics of biological networks is a fundamental step towards understanding how the nervous system works. Spontaneous activity in cultured networks of cortical neurons has been investigated by using a multisite recording technique with planar electrode arrays. In these networks, the spatiotemporal firing patterns were studied in the presence of different extracellular solutions. Transitions from asynchronous firing dynamics to synchronous firing dynamics were observed when the extracellular Ca2+ concentration was increased from 0.1 mM to 1 mM. Addition of extracellular Mg2+ reduced the spontaneous activity at any Ca2+ concentration, and an increase in the extracellular K+ concentration enhanced the frequency of periodical synchronous bursts. N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists inhibited synchronous activity. A spatiotemporal analysis of the data has been performed, and the properties of the network such as the synchronization and the periodicity have been quantified in order to clarify how variations of intrinsic parameters of the network can induce structural transitions in the neural dynamics. This experimental study is a possible approach to investigate the computational properties of a neuronal network.

Effect of BDNF on synchronous and asynchronous activity in cultured networks of cortical neurons

Effect of BDNF on synchronous and asynchronous activity in cultured networks of cortical neurons

1317 Effect of BNDF on synchronous and asynchronous activity in cultured networks of cortical neurons

The lifetime of the most recent generation micro-channel plate (MCP) PMTs of BINP, Hamamatsu (R10754X) and PHOTONIS (XP85112) is being studied in a simultaneous measurement. We find that the new techniques applied to reduce the aging of the photocathode of the MCP-PMTs has significantly increased the lifetime. Dark count rate, gain and quantum efficiency of the tubes are given as a function of the integrated anode charge. Several times the quantum efficiency was also measured across the surface of the photocathode. At this point of the ongoing measurements the best MCP-PMT turns out to be the XP85112 with its MCP surfaces coated by an atomic layer to reduce the outgassing of the lead glass. This tube shows no aging after an integrated anode charge of 2.1 C/cm2 which is more than an order of magnitude better than that of previous generation MCP-PMTs.

Spontaneous periodic synchronized bursting during formation of mature patterns of connections in cortical cultures

Long-term recording of spontaneous activity in cultured cortical neuronal networks was carried out using substrates containing multi-electrode arrays. Spontaneous uncorrelated firing appeared within the first 3 days and transformed progressively into synchronized bursting within a week. By 30 days from the establishment of the culture, the network exhibited a complicated non-periodic, synchronized activity pattern which showed no changes for more than 2 months and thus represented the mature state of the network. Pharmacological inhibition of activity only during the period when regular synchronized bursting was observed was capable of producing a different mature activity pattern from the control. These results suggest that periodic synchronized bursting plays a critical role in the development of synaptic connections.

The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons

The characteristics and mechanisms of synchronized firing in developing networks of cultured cortical neurons were studied using multisite recording through planar electrode arrays (PEAs). With maturation of the network (from 3 to 40 d after plating), the frequency and propagation velocity of bursts increased markedly (approximately from 0.01 to 0.5 Hz and from 5 to 100 mm/sec, respectively), and the sensitivity to extracellular magnesium concentration (0-10 mM) decreased. The source of spontaneous bursts, estimated from the relative delay of onset of activity between electrodes, varied randomly with each burst. Physical separation of synchronously bursting networks into several parts using an ultraviolet laser, divided synchronous bursting into different frequencies and phases in each part. Focal stimulation through the PEA was effective at multiple sites in eliciting bursts, which propagated over the network from the site of stimulation. Stimulated bursts exhibited both an absolute refractory period and a relative refractory period, in which partially propagating bursts could be elicited. Periodic electrical stimulation (at 1 to 30 sec intervals) produced slower propagation velocities and smaller numbers of spikes per burst at shorter stimulation intervals. These results suggest that the generation and propagation of spontaneous synchronous bursts in cultured cortical neurons is governed by the level of spontaneous presynaptic firing, by the degree of connectivity of the network, and by a distributed balance between excitation and recovery processes.

Developmental changes in electrical activity of cultured cortical neuronal networks

Developmental changes in electrical activity of cultured cortical neuronal networks

Synchronous oscillatory stimulation can induce change of spatial and temporal patterns of bursting in cultured cortical neuron networks

Synchronous oscillatory stimulation can induce change of spatial and temporal patterns of bursting in cultured cortical neuron networks

The inhibition of neuronal activity, the synaptic death and the neuronal death induced by glutamate in cultured cortical neuronal networks

The inhibition of neuronal activity, the synaptic death and the neuronal death induced by glutamate in cultured cortical neuronal networks

Frequency of synchronous oscillations of neuronal activity increases during development and is correlated to the number of synapses in cultured cortical neuron networks

It has been proposed that synchronous oscillations of groups of neurons corresponding to sensory information and changes in temporal pattern of oscillations are important for processing of the information in the cortex. However, it has not been determined yet how the temporal or spatial pattern of such oscillations are regulated. We observed spontaneous synchronous oscillations of Ca 2+ transients, which were caused by bursts of action potentials of neurons, even in cultured cortical neurons. The frequency of synchronous Ca 2+ oscillations increased with development of synapses in cultured neurons and was highly correlated to the number of synapses formed in the same culture.

“Probing” the nature of the CNV

A widespread depolarization in the dendritic trees of cortical pyramidal neurons generates surface-negative potentials. In turn, such potentials may indicate facilitatory processes while positive-going waves may result from a lowering in cortical excitability. Accordingly, we may expect the processing of “probe” stimuli presented during surface-positive waves, i.e., during phases of lesser excitability, to be inhibited and probes presented during surface-negative waves to be facilitated. This hypothesis was tested by presenting acoustic probe stimuli at various points in time during a forewarned reaction time task. The warming stimulus (WS) elicited a late positive complex followed by a negative slow potential shift (CNV). In 75% of the total of 120 trials a probe could be presented 1.5 sec prior to the WS interval, 0.5, 1, 1.5 or 2 sec after the onset of the 3 sec visual WS, and 3 sec following the imperative signal (WS offset, requiring a fast button press response), while 25% of the trials were without any probe. Only one probe occurred during a trial. The EEG was recorded along the midsagittal line; responses to the probes were evaluated by reaction time (RT) and probe-evoked potentials. RT to probes presented late in the anticipatory interval were speeded up and probe-evoked potentials were enhanced during this interval, in parallel to the development of the slow potential and the CNV in particular. Results suggest that probe stimuli presented during the development of the CNV were processed more intensely, thereby supporting the hypothesis that slow cortical potentials indicate the timing of excitability in cortical neuronal networks. Such a tuning mechanism may serve as a basis for attentional regulation.