NMDA Receptor-Dependent Synaptic Activation of TRPC Channels in Olfactory Bulb Granule Cells

Aroniadou-Anderjaska, Vassiliki, Matthew Ennis, and Michael T. Shipley. Current-source density analysis in the rat olfactory bulb: laminar distribution of kainate/AMPA- and NMDA-receptor-mediated currents. J. Neurophysiol. 81: 15–28, 1999. The one-dimensional current-source density method was used to analyze laminar field potential profiles evoked in rat olfactory bulb slices by stimulation in the olfactory nerve (ON) layer or mitral cell layer (MCL) and to identify the field potential generators and the characteristics of synaptic activity in this network. Single pulses to the ON evoked a prolonged (≥400 ms) sink (S1ON) in the glomerular layer (GL) with corresponding sources in the external plexiform layer (EPL) and MCL and a relatively brief sink (S2ON) in the EPL, reversing in the internal plexiform and granule cell layers. These sink/source distributions suggested that S1ON and S2ON were generated in the apical dendrites of mitral/tufted cells and granule cells, respectively. The kainate/AMPA-receptor antagonist CNQX (10 μM) reduced the early phase of S1ON, blocked S2ON, and revealed a low amplitude, prolonged sink at the location of S2ON in the EPL. Reduction of Mg2+, in CNQX, enhanced both the CNQX-resistant component of S1ON and the EPL sink. This EPL sink reversed below the MCL, suggesting it was produced in granule cells. The NMDA-receptor antagonist APV (50 μM) reversibly blocked the CNQX-resistant field potentials in all layers. Single pulses were applied to the MCL to antidromically depolarize the dendrites of mitral/tufted cells. In addition to synaptic currents of granule cells, a low-amplitude, prolonged sink (S1mcl) was evoked in the GL. Corresponding sources were in the EPL, suggesting that S1mcl was generated in the glomerular dendritic tufts of mitral/tufted cells. Both S1mcl and the granule cell currents were nearly blocked by CNQX (10 μM) but enhanced by subsequent reduction of Mg2+; these currents were blocked by APV. S1mcl also was enhanced by γ-aminobutyric acid-A-receptor antagonists applied to standard medium; this enhancement was reduced by APV. ON activation produces prolonged excitation in the apical dendrites of mitral/tufted cells, via kainate/AMPA and NMDA receptors, providing the opportunity for modulation and integration of sensory information at the first level of synaptic processing in the olfactory system. Granule cells respond to input from the lateral dendrites of mitral/tufted cells via both kainate/AMPA and NMDA receptors; however, in physiological concentrations of extracellular Mg2+, NMDA-receptor activation does not contribute significantly to the granule cell responses. The glomerular sink evoked by antidromic depolarization of mitral/tufted cell dendrites suggests that glutamate released from the apical dendrites of mitral/tufted cells may excite the same or neighboring mitral/tufted cell dendrites.

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Synaptic Activation of Ca2+ Action Potentials in Immature Rat Cerebellar Granule Cells In Situ

Journal of Neurophysiology ◽

10.1152/jn.1997.78.3.1631 ◽

1997 ◽

Vol 78 (3) ◽

pp. 1631-1642 ◽

Cited By ~ 35

Author(s):

Egidio D'Angelo ◽

Giovanna De Filippi ◽

Paola Rossi ◽

Vanni Taglietti

Keyword(s):

Nmda Receptor ◽

Granule Cell ◽

Action Potentials ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Synaptic Activation ◽

Immature Rat ◽

Cerebellar Granule ◽

Channel Dependent

D'Angelo, Egidio, Giovanna De Filippi, Paola Rossi, and Vanni Taglietti. Synaptic activation of Ca2+ action potentials in immature rat cerebellar granule cells in situ. J. Neurophysiol. 78: 1631–1642, 1997. Although numerous Ca2+ channels have been identified in cerebellar granule cells, their role in regulating excitability remained unclear. We therefore investigated the excitable response in granule cells using whole cell patch-clamp recordings in acute rat cerebellar slices throughout the time of development (P4–P21, n = 183), with the aim of identifying the role of Ca2+ channels and their activation mechanism. After depolarizing current injection, 46% of granule cells showed Ca2+ action potentials, whereas repetitive Na+ spikes were observed in an increasing proportion of granule cells from P4 to P21. Because Ca2+ action potentials were no longer observed after P21, they characterized an immature granule cell functional stage. Ca2+ action potentials consisted of an intermediate-threshold spike (ITS) activating at −60/−50 mV and sensitive to voltage inactivation and of a high-threshold spike (HTS), activating at above −30 mV and resistant to voltage inactivation. Both ITS and HTS comprised transient and protracted Ca2+ channel-dependent depolarizations. The Ca2+ action potentials could be activated synaptically by excitatory postsynaptic potentials, which were significantly slower and had a proportionately greater N-methyl-d-aspartate (NMDA) receptor-mediated component than those recorded in cells with fast repetitive Na+ spikes. The NMDA receptor current, by providing a sustained and regenerative current injection, was critical for activating the ITS, which was not self-regenerative. Moreover, NMDA receptors determined temporal summation of impulses during repetitive mossy fiber transmission, raising membrane potential into the range required for generating protracted Ca2+ channel-dependent depolarizations. The nature of Ca2+ action potentials was considered further using selective ion channel blockers. N-, L-, and P-type Ca2+ channels generated protracted depolarizations, whereas the ITS and HTS transient phase was generated by putative R-type channels (RITS and RHTS, respectively). RHTS channels had a higher activation threshold and were more resistant to voltage inactivation than RITS channels. At a mature stage, most of the Ca2+-dependent effects depended on the N-type current, which promoted spike repolarization and regulated the Na+-dependent discharge frequency. These observations relate Ca2+ channel types with specific neuronal excitable properties and developmental states in situ. Synaptic NMDA receptor-dependent activation of Ca2+ action potentials provides a sophisticated mechanism for Ca2+ signaling, which might be involved in granule cell development and plasticity.

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Investigations of non-NMDA receptor-induced toxicity in serum-free antioxidant-rich primary cultures of murine cerebellar granule cells

Neurochemistry International ◽

10.1016/s0197-0186(97)00132-0 ◽

1998 ◽

Vol 33 (1) ◽

pp. 537-542

Author(s):

F Carroll

Keyword(s):

Nmda Receptor ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Primary Cultures ◽

Cerebellar Granule ◽

Serum Free

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Group I Metabotropic Glutamate Receptors Are Differentially Expressed by Two Populations of Olfactory Bulb Granule Cells

Journal of Neurophysiology ◽

10.1152/jn.01202.2006 ◽

2007 ◽

Vol 97 (4) ◽

pp. 3136-3141 ◽

Cited By ~ 8

Author(s):

Thomas Heinbockel ◽

Kathryn A. Hamilton ◽

Matthew Ennis

Keyword(s):

Olfactory Bulb ◽

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Granule Cells ◽

Mitral Cell ◽

Mitral Cells ◽

Patch Clamp Recording ◽

Metabotropic Glutamate ◽

Group I ◽

Bath Application

In the main olfactory bulb, several populations of granule cells (GCs) can be distinguished based on the soma location either superficially, interspersed with mitral cells within the mitral cell layer (MCL), or deeper, within the GC layer (GCL). Little is known about the physiological properties of superficial GCs (sGCs) versus deep GCs (dGCs). Here, we used patch-clamp recording methods to explore the role of Group I metabotropic glutamate receptors (mGluRs) in regulating the activity of GCs in slices from wildtype and mGluR−/− mutant mice. In wildtype mice, bath application of the selective Group I mGluR agonist DHPG depolarized and increased the firing rate of both GC subtypes. In the presence of blockers of fast synaptic transmission (APV, CNQX, gabazine), DHPG directly depolarized both GC subtypes, although the two GC subtypes responded differentially to DHPG in mGluR1−/− and mGluR5−/− mice. DHPG depolarized sGCs in slices from mGluR5−/− mice, although it had no effect on sGCs in slices from mGluR1−/− mice. By contrast, DHPG depolarized dGCs in slices from mGluR1−/− mice but had no effect on dGCs in slices from mGluR5−/− mice. Previous studies showed that mitral cells express mGluR1 but not mGluR5. The present results therefore suggest that sGCs are more similar to mitral cells than dGCs in terms of mGluR expression.

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Migration of bipolar subependymal cells, precursors of the granule cells of the rat olfactory bulb, with reference to the arrangement of the radial glial fibers.

Archives of Histology and Cytology ◽

10.1679/aohc.53.219 ◽

1990 ◽

Vol 53 (2) ◽

pp. 219-226 ◽

Cited By ~ 46

Author(s):

Kiyoshi KISHI ◽

Jun Yun PENG ◽

Sachiko KAKUTA ◽

Kunio MURAKAMI ◽

Masaru KURODA ◽

...

Keyword(s):

Olfactory Bulb ◽

Granule Cells ◽

Radial Glial

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The Mitral and Short Axon Cells of the Olfactory Bulb

Journal of Cell Science ◽

10.1242/jcs.7.3.631 ◽

1970 ◽

Vol 7 (3) ◽

pp. 631-651

Author(s):

J. L. PRICE ◽

T. P. S. POWELL

Keyword(s):

Electron Microscope ◽

Olfactory Bulb ◽

Granule Cells ◽

Primary Dendrite ◽

Plexiform Layer ◽

Mitral Cell ◽

Granule Cell Layer ◽

Mitral Cells ◽

Axon Initial Segments ◽

Large Neurons

A description is given of the mitral and short axon cells of the olfactory bulb of the rat from Golgi material examined with the light microscope and from material examined with the electron microscope. The mitral cells are large neurons with primary and secondary dendrites which both extend into the overlying external plexiform layer, although only the primary dendrite enters the glomerular formations. No predominant antero-posterior orientation of the secondary dendrites has been found. Within the glomeruli the mitral cell dendrites are in synaptic contact with the olfactory nerves and also with the periglomerular cells, but elsewhere the only synapses on the mitral cells are the ‘reciprocal synapses’ with the granule cells. Synaptic-type vesicles are found in all parts of the mitral cells, including the axon initial segments; they appear to be especially concentrated in the distal portions of the dendrites. Several types of short axon cells have been found in the granule cell layer in Golgi-impregnated material. Their cell bodies can also be distinguished with the electron microscope, and from previous work it is probable that the axons of at least some of these cells form flattened-vesicle symmetrical synapses upon the granule cells.

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Transient Activity Induces a Long-Lasting Increase in the Excitability of Olfactory Bulb Interneurons

Journal of Neurophysiology ◽

10.1152/jn.00526.2007 ◽

2008 ◽

Vol 99 (1) ◽

pp. 187-199 ◽

Cited By ~ 8

Author(s):

Tsuyoshi Inoue ◽

Ben W. Strowbridge

Keyword(s):

Olfactory Bulb ◽

Granule Cells ◽

Receptor Activation ◽

Brain Regions ◽

Persistent Activity ◽

Cellular Mechanisms ◽

Calcium Dependent ◽

Transient Activity ◽

Olfactory Bulb Slices ◽

Processing And Storage

Little is known about the cellular mechanisms that underlie the processing and storage of sensory in the mammalian olfactory system. Here we show that persistent spiking, an activity pattern associated with working memory in other brain regions, can be evoked in the olfactory bulb by stimuli that mimic physiological patterns of synaptic input. We find that brief discharges trigger persistent activity in individual interneurons that receive slow, subthreshold oscillatory input in acute rat olfactory bulb slices. A 2- to 5-Hz oscillatory input, which resembles the synaptic drive that the olfactory bulb receives during sniffing, is required to maintain persistent firing. Persistent activity depends on muscarinic receptor activation and results from interactions between calcium-dependent afterdepolarizations and low-threshold Ca spikes in granule cells. Computer simulations suggest that intrinsically generated persistent activity in granule cells can evoke correlated spiking in reciprocally connected mitral cells. The interaction between the intrinsic currents present in reciprocally connected olfactory bulb neurons constitutes a novel mechanism for synchronized firing in subpopulations of neurons during olfactory processing.

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