Synchronous neuronal oscillations in the 30-70 Hz range, known as gamma oscillations, occur in the cortex of many species. This synchronization can occur over large distances, and in some cases over multiple cortical areas and in both hemispheres; it has been proposed to underlie the binding of several features into a single perceptual entity. The mechanism by which coherent oscillations are generated remains unclear, because they often show zero or near-zero phase lags over long distances, whereas much greater phase lags would be expected from the slow speed of axonal conduction. We have previously shown that interneuron networks alone can generate gamma oscillations; here we propose a simple model to explain how an interconnected chain of such networks can generate coherent oscillations. The model incorporates known properties of excitatory pyramidal cells and inhibitory interneurons; it predicts that when excitation of interneurons reaches a level sufficient to induce pairs of spikes in rapid succession (spike doublets), the network will generate gamma oscillations that are synchronized on a millisecond time-scale from one end of the chain to the other. We show that in rat hippocampal slices interneurons do indeed fire spike doublets under conditions in which gamma oscillations are synchronized over several millimetres, whereas they fire single spikes under other conditions. Thus, known properties of neurons and local synaptic circuits can account for tightly synchronized oscillations in large neuronal ensembles.
We used transverse and longitudinal rat hippocampal slices to study the synchronization of γ frequency (> 20 Hz) oscillations, across distances of up to 4.5 mm. γ oscillations were evoked in the CA1 region by tetanic stimulation at one or two sites simultaneously, and were associated with population spikes. Tetanic stimuli that were strong enough to induce oscillations were associated with depolarization of both pyramidal cells and interneurones, largely produced by activation of metabotropic glutamate receptors. Computer simulations of γ oscillations were also performed in a model with pyramidal cells and interneurones, arranged in a chain of five cell groups. This model had suggested previously that interneurone networks alone could generate synchronous γ oscillations locally, but that pyramidal cell firing, by inducing spike doublets in interneurones, was necessary for the occurrence of highly correlated oscillations with small phase lag (< 2.5 ms), in a distributed network possessing long axon conduction delays. In both experiment and model, pyramidal cell spikes occurred in phase with local population spikes, as did the first spike of the interneurone doublet. The conductance of the interneurone α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor‐mediated conductance was manipulated in the model, while the relation between oscillations at opposite ends of the chain was examined. When the conductance was large enough for doublet firing to be synaptically induced in interneurones, oscillation phase lags were < 2.25 ms across the chain. As predicted, experimental blockade of AMPA receptors resulted in increased phase lags between two sites oscillating simultaneously, compared with control conditions. Both in model and in experiment, when stimuli to the two ends of the network were slightly different, cross‐network synchronization occurred with a shorter phase lag at high frequencies than at lower frequencies. These data suggest that, while interneurone networks alone can generate locally synchronized γ oscillations, firing of pyramidal cells, and the synaptically induced doublet firing in interneurones, contribute to the stability and tight synchrony of the oscillations in distributed networks.
1. Neurones of the globus pallidus (GP) have been classified into three subgroups based on the visual inspection of current clamp electrophysiological properties and morphology of biocytin-filled neurones. 2. Type A neurones (132Ï208; 63%) were identified by the presence of the time-and voltagedependent inward rectifier (Ih) and the low-threshold calcium current (It) giving rise to anodal break depolarisations. These cells were quiescent or fired regular spontaneous action potentials followed by biphasic AHPs. Current injection evoked regular activity up to maximum firing frequency of 350 Hz followed by moderate spike frequency adaptation. The somata of type A cells were variable in shape (20 ² 12 ìm) while their dendrites were highly varicose. 3. Type B neurones (66Ï208; 32%) exhibited neither Ih nor rebound depolarisations and only a fast monophasic AHP. These cells were spontaneously active while current injection induced irregular patterns of action potential firing up to a frequency of 440 Hz with weak spike frequency adaptation. Morphologically, these cells were the smallest encountered (15 ² 10 ìm), oval in shape with restricted varicose dendritic arborisations. 4. Type C neurones were much rarer (10Ï208; 5%). They were identified by the absence of Ih and rebound depolarisations, but did possess a prolonged biphasic AHP. They displayed large A-like potassium currents and ramp-like depolarisations in response to step current injections, which induced firing up to a maximum firing frequency of 310 Hz. These cells were the largest observed (27 ² 15 ìm) with extensive dendritic branching. 5. These results confirm neuronal heterogeneity in the adult rodent GP. The driven activity and population percentage of the three subtypes correlates well with the in vivo studies (Kita & Kitai, 1991). Type A cells appear to correspond to type II neurones of Nambu & Llinas (1994, 1997 while the small diameter type B cells display morphological similarities with those described by Millhouse (1986). The rarely encountered type C cells may well be large cholinergic neurones. These findings provide a cellular basis for the study of intercellular communication and network interactions in the adult rat in vitro. Keywords:
Gamma frequency (about 20-70 Hz) oscillations occur during novel sensory stimulation, with tight synchrony over distances of at least 7 mm. Synchronization in the visual system has been proposed to reflect coactivation of different parts of the visual field by a single spatially extended object. We have shown that intracortical mechanisms, including spike doublet firing by interneurons, can account for tight long-range synchrony. Here we show that synchronous gamma oscillations in two sites also can cause long-lasting (>1 hr) potentiation of recurrent excitatory synapses. Synchronous oscillations lasting >400 ms in hippocampal area CA1 are associated with an increase in both excitatory postsynaptic potential (EPSP) amplitude and action potential afterhyperpolarization size. The resulting EPSPs stabilize and synchronize a prolonged beta frequency (about 10-25 Hz) oscillation. The changes in EPSP size are not expressed during non-oscillatory behavior but reappear during subsequent gamma-oscillatory events. We propose that oscillation-induced EPSPs serve as a substrate for memory, whose expression either enhances or blocks synchronization of spatially separated sites. This phenomenon thus provides a dynamical mechanism for storage and retrieval of stimulus-specific neuronal assemblies.Fast gamma-frequency oscillations in discrete neuronal populations have been linked to aspects of higher cognitive function, in particular, the selection and ''binding'' together of pertinent aspects of a sensory stimulus into a perceived whole (1, 2). The evidence for this link stems from the observation of these oscillations in cortical regions and cell populations devoted to the processing of sensory information of different modalities (3-5) and their ability to provide a framework for controlling temporal interactions between spatially discrete areas (6, 7). What still remains to be elucidated is whether this correlate of novel sensory processing is in any way linked to subsequent memory formation.The rat CA1 hippocampal region in vitro has proven useful for studying the cellular mechanisms underlying synchronized gamma-frequency oscillations. It possesses numerous synaptically interconnected inhibitory interneurons (8), which oscillate as a population at gamma frequencies on tonic excitation (9). It also has well developed recurrent inhibitory connections that allow excitatory pyramidal cells both to influence the firing of interneuron networks and to be influenced by these same inhibitory networks (Fig. 1A). In addition, a small number of recurrent excitatory connections from pyramidal cell to pyramidal cell occur (10). Most conventional models of memory formation involve the selective long-term enhancement of excitatory synaptic activity (11) to provide a favored pattern of neuronal intercommunication on representation of the original stimulus (12). Were pyramidal cell to pyramidal cell connections to be selectively inducible in CA1, not only would this suggest a possible memory mechanism, perhaps relevant to perception...
The ability of serotonin to modulate GABA-mediated synaptic input to substantia nigra pars reticulata (SNr) neurons was investigated with the use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABA(A) receptor-mediated synaptic currents (IPSCs) were attenuated reversibly approximately 60% by serotonin, which also caused an inward current with reversal potential of -25 mV. This inward current was blocked by the 5-HT2 receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT1B receptor antagonist pindolol. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABA(B) receptor agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tetrodotoxin-sensitive GABA(A) synaptic currents (sIPSCs) were increased in frequency by serotonin (an action that was sensitive to ritanserin, but not pindolol) but reduced in frequency by baclofen. SNr neurons therefore receive inhibitory synaptic input mediated by GABA(A) receptors from at least two distinct sources. One, probably originating from the striatum, may be depressed via presynaptic 5-HT1B and GABA(B) receptors. The second is likely to arise from axon collaterals of SNr neurons themselves and is facilitated by an increase in firing via postsynaptic, somatodendritic 5-HT2C receptor activation, but it is depressed by GABA(B) receptor activation. Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.