Serviços Personalizados
Journal
Artigo
nova página do texto(beta)
Espanhol (pdf)
Artigo em XML
Referências do artigo
Tradução automática
Enviar este artigo por emailIndicadores
-
Citado por SciELO -
Acessos
Links relacionados
-
Similares em
SciELO
Compartilhar
Permalink
Salud mental
versão impressa ISSN 0185-3325
Salud Ment vol.30 no.2 México Mar./Abr. 2007
Artículos originales
Las bases celulares de las oscilaciones neuronales
*Alumno del Programa de Doctorado en Ciencias Biomédicas del Instituto de Fisiología Celular. UNAM, Apartado Postal 04510, México D.F.
**Profesor Titular del Departamento de Fisiología, Biofísica y Neurociencias. CINVESTAV.
Una de las características de los circuitos neuronales es que sus componentes, las neuronas, pueden presentar actividad eléctrica sincrónica y, gracias a ésta, generar actividad oscilatoria. Esta actividad se ha asociado a diversas funciones fisiológicas como el procesamiento de información sensorial, la memoria, el ciclo vigiliasueño y la conciencia. La actividad oscilatoria de un circuito neuronal está mediada por i) las propiedades intrínsecas de sus células, ii) la arquitectura de sus conexiones y iii) la dinámica de sus interacciones sinápticas. A nivel celular, las señales sinápticas pueden generar oscilaciones subumbrales del potencial de membrana y regular la frecuencia de disparo. Estas oscilaciones modulan la respuesta celular a las entradas sinápticas que ocurren en frecuencias funcionalmente relevantes y que, finalmente, producen los diferentes ritmos cerebrales.
A nivel estructural, el conjunto de proyecciones axonales de corto, mediano y largo alcance, permiten que módulos discretos, pero interconectados, oscilen en sincronía a lo largo de amplias regiones cerebrales.
En esta revisión, resaltamos la importancia que tienen las interacciones sinápticas, excitadora e inhibidora, en la regulación y mantenimiento de la sincronía del disparo en grupos neuronales. Abordamos también el impacto de la plasticidad de corto y largo plazo de la transmisión GABAérgica en la modulación de las propiedades sinápticas, las oscilaciones neuronales y su participación en la generación de ritmos hiper-sincrónicos, asociados con las descargas epilépticas y las alteraciones que éstas últimas producen en los mecanismos de inhibición sináptica. Por ejemplo, después de una crisis convulsiva generalizada o de inducir un estado de hiperexcitación, las células granulares glutamatérgicas del giro dentado del hipocampo, presentan modificaciones que les permiten sintetizar y liberar GABA, que actúa sobre receptores pre- y postsinápticos.
En este escenario, el GABA liberado espontáneamente de las células granulares, inhibe las oscilaciones de ~20 Hz en la zona CA3 del hipocampo. Se ha propuesto que este mecanismo, activado por crisis convulsivas, podría servir para limitar la actividad de la red neuronal en respuesta a incrementos de excitabilidad. De igual forma, su presencia se ha asociado con los efectos deletéreos que tienen las crisis convulsivas sobre el aprendizaje y la consolidación de memoria, particularmente durante la fase post-ictal. Finalmente discutimos el posible papel computacional que las oscilaciones neuronales tienen en la representación de información sensorial.
Palabras clave: Oscilaciones neuronales; oscilaciones subumbrales; sincronía; redes neuronales; plasticidad GABAérgica
Neuronal oscillations emerge as a consequence of the interaction of large groups of neurons, which can synchronize their activity to generate a rhythmic field behavior. They occur in different brain areas and have been associated to relevant physiological and pathological processes such as sensory processing, memory, epilepsy and consciousness.
Neuronal oscillations are mediated and shaped by i) the intrinsic properties of the cell membrane, ii) the architecture of synaptic connections between the neurons confined in a network, and iii) the dynamics of the synaptic currents. The firing properties of the neurons depend on the ionic channels that they possess but nonlinear interactions between different families of ionic currents, may produce small subthreshold membrane oscillations (SMOs).
Because the probability to generate an action potential rises during the depolarizing phase of the SMOs, this activity can regulate the neuron’s firing frequency. Consequently, SMOs influence the responsiveness of the neuron to synaptic inputs that occur at particular frequencies and which, finally, produce a broad range of brain rhythms. In addition to the intrinsic properties of the neuronal membrane, the firing frequency of single neurons depends on the synaptic inputs from other neurons within the network. Indeed, neurons can produce responses in their neighbors by means of electrical and chemical synapses. In this sense, two or more neurons are in synchrony if each fires action potentials, within a small time window before or after the other. This could be explained if both neurons share the same synaptic input or if they interact with each other. Hence, network synchrony is reflected by the current flow between the extracellular and intracellular compartments which can be recorded as a field potential in the extracellular space.
Thus, this field potential reflects both synchronic subthreshold events and action potentials generated by the cells contained in the recorded field. Therefore, the electric potential produced by the synchronized activity of cortical neurons can be recorded over the scalp (the electroencephalogram or EEG). This activity is characterized by its morphology, its frequency and the experimental context in which it is recorded.
The cortical brain rhythms are classified in frequency bands, and they are associated with different brain states. They compete and interact with each other and can coexist in the same or in different structures. Because field oscillations can be spontaneously generated in vitro, their generating and sustaining mechanisms can be thoroughly studied. For instance, blockade of presynaptic or postsynaptic receptors is a common tool used to isolate the specific contributions of different synaptic components that generate the field oscillations.
We also discuss the role of short and long-term GABAergic plasticity and its involvement in neuronal oscillations and in the generation of hyper-synchronic rhythms that underlie epileptic discharges. Indeed, excitatory and inhibitory synaptic interactions regulate and sustain the firing synchrony in neural networks. For instance, diverse sets of GABAergic interneurons contribute with different firing frequencies that finally inhibit their postsynaptic targets: excitatory principal cells and other interneurons. In other words, inhibitory synapses, as a whole, generate different synchronic neuronal events and restrain the network excitability. Hence, it is relevant to study which parameters do modify the GABAergic transmission. For instance, a feature of GABAergic synapses is that prolonged GABAA-R activation may lead to a switch from a hyperpolarizing to a depolarizing postsynaptic response. This is partly due to a positive shift on the GABAA-R reversal potential (EGABA) because of a GABA-induced-chloride (Cl-) accumulation in the postsynaptic neurons.
Recent studies suggest that the activity-dependent EGABA shift may have important implications in the mechanisms involved in the generation of γ (~40 Hz) oscillations and seizure-like discharges. The study of how intracellular Cl- dynamics shape network oscillations may bring insights into the mechanisms of physiological and pathological brain rhythms. Moreover, Cl- dynamics have also prominent functional implications during development.
Another relevant example of GABAergic plasticity is observed in the glutamatergic hippocampal granule cells (GCs). In response to an increment in network excitability, GCs are able to synthesize and release GABA for fast neurotransmission. Several experimental results have compellingly shown that GABAergic signaling from these cells activates presynaptic and postsynaptic GABAergic receptors. Therefore, it is plausible that after seizures, the GCs could spontaneously release GABA that would, in turn, change the spontaneous field activity that naturally emerges from the postsynaptic targets that comprise the CA3 intrinsic network oscillator. And this is indeed the case. GABA released from CGs inhibits β/γ oscillations (~20 Hz) in the CA3 area, where principal cells and interneurons are impinged by CGs. Thus, this mechanism could be used to limit network excitability after seizures. The emergence of the GABAergic phenotype in CGs could also be involved in the deleterious effects on learning and memory consolidation that have been observed after seizures. Finally, we briefly discuss the computational role that network oscillations may have to represent sensory information.
Key words: Neuronal oscillations; subthreshold oscillations; synchrony; neural networks; GABAergic plasticity
Referencias
1. ALONSO A, LLINAS RR: Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II. Nature, 342:175-177, 1989. [ Links ]
2. ANDERSEN P, ANDERSSON SA, JUNGE K, SVEEN O: Patterns of spontaneous barbturate spindle activity within the thalamus. Electroencephalogr Clin Neurophysiol, 24:90, 1968. [ Links ]
3. BARNARD EA, SKOLNICK P, OLSEN RW, MOHLER H, SIEGHART W y cols.: International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev, 50:291-313, 1998. [ Links ]
4. BARTOS M, VIDA I, FROTSCHER M, MEYER A y cols.: Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks. Proc Natl Acad Sci USA, 99:13222-13227, 2002. [ Links ]
5. BUZSAKI G: Functions for interneuronal nets in the hippocampus. Can J Physiol Pharmacol, 75:508-515, 1997. [ Links ]
6. BUZSAKI G, CHROBAK JJ: Temporal structure in spatially organized neuronal ensembles: a role for interneuronal networks. Curr Opin Neurobiol, 5:504-510, 1995. [ Links ]
7. BUZSAKI G, GEISLER C, HENZE DA, WANG XJ: Interneuron Diversity series: Circuit complexity and axon wiring economy of cortical interneurons. Trends Neurosci, 27:186-193, 2004. [ Links ]
8. BUZSAKY G: Rhythms of the Brain. Oxford University Press, Oxford, 2006. [ Links ]
9. CASTELO-BRANCO M, GOEBEL R, NEUENSCHWANDER S, SINGER W: Neural synchrony correlates with surface segregation rules. Nature, 405:685-689, 2000. [ Links ]
10. COBB SR, BUHL EH, HALASY K, PAULSEN O, SOMOGYI P: Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature, 378:75-78, 1995. [ Links ]
11. DESTEXHE A, CONTRERAS D, STERIADE M: Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states. J Neurosci, 19:4595-4608, 1999. [ Links ]
12. DESTEXHE A, MAINEN ZF, SEJNOWSKI TJ: Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J Comput Neurosci, 1:195-230, 1994. [ Links ]
13. DRAGUHN A, TRAUB RD, SCHMITZ D, JEFFERYS JG: Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature, 394:189-192, 1998. [ Links ]
14. ENGEL AK, FRIES P, SINGER W: Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci, 2:704-716, 2001. [ Links ]
15. FISAHN A, PIKE FG, BUHL EH, PAULSEN O: Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro. Nature, 394:186-189, 1998. [ Links ]
16. GIBSON JR, BEIERLEIN M, CONNORS BW: Two networks of electrically coupled inhibitory neurons in neocortex. Nature, 402:75-79, 1999. [ Links ]
17. GLYKYS J, MODY I: Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABA A receptor alpha5 subunit-deficient mice. J Neurophysiol, 95:2796-2807, 2006. [ Links ]
18. GOLSHANI P, LIU XB, JONES EG: Differences in quantal amplitude reflect GluR4- subunit number at corticothalamic synapses on two populations of thalamic neurons. Proc Natl Acad Sci USA, 98:4172-4177, 2001. [ Links ]
19. GOMEZ-LIRA G, LAMAS M, ROMO-PARRA H, GUTIERREZ R: Programmed and induced phenotype of the hippocampal granule cells. J Neurosci, 25:6939-6946, 2005. [ Links ]
20. GOMEZ-LIRA G, TRILLO E, RAMIREZ M, ASAI M, SITGES M, GUTIERREZ R: The expression of GABA in mossy fiber synaptosomes coincides with the seizure-induced expression of GABAergic transmission in the mossy fiber sy18 Salud Mental, Vol. 30, No. 2, marzo-abril 2007 napse. Exp Neurol, 177:276-283, 2002. [ Links ]
21. GUTIERREZ R: Activity-dependent expression of simultaneous glutamatergic and GABAergic neurotransmission from the mossy fibers in vitro. J Neurophysiol, 87:2562-2570, 2002. [ Links ]
22. GUTIERREZ R: The GABAergic phenotype of the "glutamatergic " granule cells of the dentate gyrus. Prog Neurobiol, 71:337-358, 2003. [ Links ]
23. GUTIERREZ R: The dual glutamatergic-GABAergic phenotype of hippocampal granule cells. Trends Neuroscience, 28:297-303, 2005. [ Links ]
24. GUTIERREZ R, TREVINO M, VIVAR C: Initially Glutamatergic, Mossy Fibres are also GABAergic after Seizures. Epilepsia, 46:38, 2005. [ Links ]
25. HARRIS KD, CSICSVARI J, HIRASE H, DRAGOI G, BUZSAKI G: Organization of cell assemblies in the hippocampus. Nature, 424:552-556, 2003. [ Links ]
26. HEINEMANN U, BECK H, DREIER JP, FICKER E, STABEL J,ZHANG CL: The dentate gyrus as a regulated gate for the propagation of epileptiform activity. Epilepsy Res (Supl), 7:273-280, 1992. [ Links ]
27. HUTCHEON B, YAROM Y: Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci, 23:216-222, 2000. [ Links ]
28. JAROLIMEK W, LEWEN A, MISGELD U: A furosemidesensitive K+-Cl- cotransporter counteracts intracellular Claccumulation and depletion in cultured rat midbrain neurons. J Neurosci, 19:4695-4704, 1999. [ Links ]
29. KAILA K, VOIPIO J: Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance. Nature, 330:163-165, 1987. [ Links ]
30. KORPI ER, GRUNDER G, LUDDENS H: Drug interactions at GABA(A) receptors. Prog Neurobiol, 67:113-159, 2002. [ Links ]
31. LAMAS M, GOMEZ-LIRA G, GUTIERREZ R: Vesicular GABA transporter mRNA expression in the dentate gyrus and in mossy fiber synaptosomes. Brain Res Mol Brain Res, 93:209-214, 2001. [ Links ]
32. LAMPL I, YAROM Y: Subthreshold oscillations and resonant behavior: two manifestations of the same mechanism. Neuroscience, 78:325-341, 1997. [ Links ]
33. LISMAN JE, IDIART MA: Storage of 7 +/- 2 short-term memories in oscillatory subcycles. Science, 267:1512-1515, 1995. [ Links ]
34. LLINAS R, RIBARY U, CONTRERAS D, PEDROARENA C: The neuronal basis for consciousness. Philos Trans R Soc Lond B Biol Sci, 353:1841-1849, 1998. [ Links ]
35. LLINAS RR: The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science, 242:1654-1664, 1988. [ Links ]
36. LYTTON WW, SEJNOWSKI TJ: Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons. J Neurophysiol, 66:1059-1079, 1991. [ Links ]
37. MACLEOD K, BACKER A, LAURENT G: Who reads temporal information contained across synchronized and oscillatory spike trains? Nature, 395:693-698, 1998. [ Links ]
38. MAKARENKO V, LLINAS R: Experimentally determined chaotic phase synchronization in a neuronal system. Proc Natl Acad Sci USA, 95:15747-15752, 1998. [ Links ]
39. MITZDORF U: Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. Physiol Rev, 65:37-100, 1985. [ Links ]
40. O'KEEFE J: Place units in the hippocampus of the freely moving rat. Exp Neurol, 51:78-109, 1976. [ Links ]
41. O'KEEFE J, RECCE ML: Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus, 3:317-330, 1993. [ Links ]
42. PAPE HC, DRIESANG RB: Ionic mechanisms of intrinsic oscillations in neurons of the basolateral amygdaloid complex. J Neurophysiol, 79:217-226, 1998. [ Links ]
43. PUIL E, GIMBARZEVSKY B, MIURA RM: Quantification of membrane properties of trigeminal root ganglion neurons in guinea pigs. J Neurophysiol, 55:995-1016, 1986. [ Links ]
44. RAMIREZ M, GUTIERREZ R: Activity-dependent expression of GAD67 in the granule cells of the rat hippocampus. Brain Res, 917:139-146, 2001. [ Links ]
45. RIVERA C, VOIPIO J, KAILA K: Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII. J Physiol, 562:27-36, 2005. [ Links ]
46. SANDLER R, SMITH AD: Coexistence of GABA and glutamate in mossy fiber terminals of the primate hippocampus: an ultrastructural study. J Comp Neurol, 303:177-192, 1991. [ Links ]
47. SANHUEZA M, BACIGALUPO J: Intrinsic subthreshold oscillations of the membrane potential in pyramidal neurons of the olfactory amygdala. Eur J Neurosci, 22:1618-1626, 2005. [ Links ]
48. SEMYANOV A, WALKER MC, KULLMANN DM, SILVER RA: Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci, 27:262-269, 2004. [ Links ]
49. SINGER W: Synchronization of cortical activity and its putative role in information processing and learning. Annu Rev Physiol, 55:349-374, 1993. [ Links ]
50. SLOVITER RS, DICHTER MA, RACHINSKY TL, DEAN E y cols.: Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J Comp Neurol, 373:593-618, 1996. [ Links ]
51. SLOVITER RS, DICHTER MA, RACHINSKY TL, DEAN E y cols.: Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J Comp Neurol, 373:593-618, 1996. [ Links ]
52. SOMOGYI P, KLAUSBERGER T: Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol, 562:9-26, 2005. [ Links ]
53. STALEY KJ, PROCTOR WR: Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cland. J Physiol, 519 Pt 3:693-712, 1999. [ Links ]
54. STERIADE M: Impact of network activities on neuronal properties in corticothalamic systems. J Neurophysiol, 86:1-39, 2001. [ Links ]
55. STERIADE M, DESCHENES M: The thalamus as a neuronal oscillator. Brain Res, 320:1-63, 1984. [ Links ]
56. STERIADE M, DESCHENES M, DOMICH L, MULLE C: Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami. J Neurophysiol, 54:1473-1497, 1985. [ Links ]
57. TRAUB RD, BIBBIG A, LEBEAU FE, BUHL EH, WHITTINGTON MA: Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro. Annu Rev Neurosci, 27:247-278, 2004. [ Links ]
58. TRAUB RD, KOPELL N, BIBBIG A, BUHL EH, LEBEAU FE, WHITTINGTON MA: Gap junctions between interneuron dendrites can enhance synchrony of gamma oscillations in distributed networks. J Neurosci, 21:9478-9486, 2001. [ Links ]
59. TRAUB RD, WHITTINGTON MA, STANFORD IM, JEFFERYS JG: A mechanism for generation of long-range synchronous fast oscillations in the cortex. Nature, 383:621-624, 1996. [ Links ]
60. TREVIÑO M, GUTIERREZ R: The GABAergic projection of the dentate gyrus to hippocampal area CA3 of the rat: preand postsynaptic actions after seizures. J Physiol, 567:939-949, 2005. [ Links ]
61. TSODYKS MV, SKAGGS WE, SEJNOWSKI TJ, MCNAUGHTON BL: Population dynamics and theta rhythm phase precession of hippocampal place cell firing: a spiking neuron model. Hippocampus, 6:271-280, 1996. [ Links ]
62. VIDA I, BARTOS M, JONAS P: Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates. Neuron, 49:107-117, 2006. [ Links ]
63. WANG XJ, BUZSAKI G: Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci, 16:6402-6413, 1996. [ Links ]
64. WHITTINGTON MA, TRAUB RD, JEFFERYS JG: Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation. Nature, 373:612-615, 1995. [ Links ]
Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons
