Limits...
Reorganization of supramammillary-hippocampal pathways in the rat pilocarpine model of temporal lobe epilepsy: evidence for axon terminal sprouting.

Soussi R, Boulland JL, Bassot E, Bras H, Coulon P, Chaudhry FA, Storm-Mathisen J, Ferhat L, Esclapez M - Brain Struct Funct (2014)

Bottom Line: This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE.This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy.It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG.

View Article: PubMed Central - PubMed

Affiliation: INSERM, UMR 1106, Institut de Neurosciences des Systèmes - INS, 13385, Marseille, France.

ABSTRACT
In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate from a multi-structural epileptogenic zone, including several regions of the limbic system connected to the hippocampal formation. In this study, we investigate the structural connectivity between the supramammillary nucleus (SuM) and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the rat. This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents originating from the SuM in pilocarpine-treated rats. This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy. It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG. This reorganization, which reflects an axon terminal sprouting from SuM neurons, could contribute to trigger spontaneous seizures within an altered hippocampal intrinsic circuitry.

No MeSH data available.


Related in: MedlinePlus

Synaptic targets of ectopic dentate gyrus afferents from SuM neurons in pilocarpine-treated rats. a–h Comparison of distribution patterns of VGLUT2-containing terminals (brown) and NeuN-labeled dentate granule cells (red) in coronal sections of the dorsal DG from a control rat (a, b) and pilocarpine-treated animals at 2 weeks (c, d), 2 months (e, f) and 12 months (g, h). b, d, f, h High magnifications of outlined areas, respectively, illustrated in panels a, c, e and g. In pilocarpine-treated rats (c–h), the distribution pattern of dentate granule cell somata was similar to that observed in the control animal (a, b). No dispersion or bi-lamination of granule cells was associated with the aberrant VGLUT2-immunolabeling observed in the IML in pilocarpine-treated rat from 2 weeks on. i A section of dorsal DG from an epileptic animal at 2 months that was injected into the CA3 stratum lucidum of the dorsal hippocampus with the Rabies virus (RV) retrograde tracer to label cell bodies and dendritic trees of dentate granule cells (G). j–k Image corresponding to a maximum intensity projection of a confocal slice z-stack (20 optical slices, spaced at 296 nm) showing labeling for the RV (green), VGAT (red) and VGLUT2 (blue) in the dorsal dentate gyrus of an epileptic rat at 2 month after pilocarpine injection. j High magnification of the region indicated by an arrow and a star in panel (i). Presumed axon terminals from SuM neurons, labeled for VGAT and VGLUT2, displayed an aberrant distribution with many boutons present in the entire IML including the upper part. Note that in the epileptic rat, the proximal apical dendrites (arrow) of dentate granule cells (*) across the IML displayed a low number of spines as compared to more distal segment. k Higher magnification of the outlined region indicated in panel j showing a dendritic tree of dentate granule cell across the upper IML contacted by ectopic VGLUT2/VGAT-containing axon terminals. l, m Images of the three different fluorophores used for the triple labeling, obtained by sequential acquisitions of separate wavelength channels from a single confocal slice, in the two outlined regions of the IML indicated in panel k and demonstrating that ectopic axon terminals labeled for VGAT (red, arrowhead) and VGLUT2 (blue, arrowhead), presumably originating from the SuM establish contact on the dendritic shafts of dentate granule cells retrogradely labeled with rabies virus (green). Scale bars 200 µm in a, c, e and g; 50 µm in b, d, f and h; 100 µm in i; 15 µm in j; 1 µm in k; 0.5 µm in l, m
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4481331&req=5

Fig7: Synaptic targets of ectopic dentate gyrus afferents from SuM neurons in pilocarpine-treated rats. a–h Comparison of distribution patterns of VGLUT2-containing terminals (brown) and NeuN-labeled dentate granule cells (red) in coronal sections of the dorsal DG from a control rat (a, b) and pilocarpine-treated animals at 2 weeks (c, d), 2 months (e, f) and 12 months (g, h). b, d, f, h High magnifications of outlined areas, respectively, illustrated in panels a, c, e and g. In pilocarpine-treated rats (c–h), the distribution pattern of dentate granule cell somata was similar to that observed in the control animal (a, b). No dispersion or bi-lamination of granule cells was associated with the aberrant VGLUT2-immunolabeling observed in the IML in pilocarpine-treated rat from 2 weeks on. i A section of dorsal DG from an epileptic animal at 2 months that was injected into the CA3 stratum lucidum of the dorsal hippocampus with the Rabies virus (RV) retrograde tracer to label cell bodies and dendritic trees of dentate granule cells (G). j–k Image corresponding to a maximum intensity projection of a confocal slice z-stack (20 optical slices, spaced at 296 nm) showing labeling for the RV (green), VGAT (red) and VGLUT2 (blue) in the dorsal dentate gyrus of an epileptic rat at 2 month after pilocarpine injection. j High magnification of the region indicated by an arrow and a star in panel (i). Presumed axon terminals from SuM neurons, labeled for VGAT and VGLUT2, displayed an aberrant distribution with many boutons present in the entire IML including the upper part. Note that in the epileptic rat, the proximal apical dendrites (arrow) of dentate granule cells (*) across the IML displayed a low number of spines as compared to more distal segment. k Higher magnification of the outlined region indicated in panel j showing a dendritic tree of dentate granule cell across the upper IML contacted by ectopic VGLUT2/VGAT-containing axon terminals. l, m Images of the three different fluorophores used for the triple labeling, obtained by sequential acquisitions of separate wavelength channels from a single confocal slice, in the two outlined regions of the IML indicated in panel k and demonstrating that ectopic axon terminals labeled for VGAT (red, arrowhead) and VGLUT2 (blue, arrowhead), presumably originating from the SuM establish contact on the dendritic shafts of dentate granule cells retrogradely labeled with rabies virus (green). Scale bars 200 µm in a, c, e and g; 50 µm in b, d, f and h; 100 µm in i; 15 µm in j; 1 µm in k; 0.5 µm in l, m

Mentions: The distribution pattern of VGLUT2 immunolabeling associated with that of NeuN-labeled dentate granule cells was analyzed in control (Fig. 7a, b) and pilocarpine-treated animals at 2 weeks (Fig. 7c, d), 2 months (Fig. 7e, f) and 12 months (Fig. 7g, h). No dispersion or bi-laminar organization of dentate granule cells correlated with the aberrant pattern of VGLUT2-containing terminals in the IML of all pilocarpine-treated rats examined (Fig. 7c–h). The thickness of the dentate granule cell layer was relatively similar in control and pilocarpine-treated rats, even though dentate granule cells in pilocarpine-treated animals displayed a decreased labeling intensity for NeuN (Fig. 7c–h) compared to control rats (Fig. 7a, b). Virtually no NeuN-labeled cell body was evident in the IML of pilocarpine-treated animals displaying increased number of VGLUT2-containing terminals at 2 weeks (Fig. 7c, d), 2 months (Fig. 7e, f) and 12 months (Fig. 7g, h) after pilocarpine injection.Fig. 7


Reorganization of supramammillary-hippocampal pathways in the rat pilocarpine model of temporal lobe epilepsy: evidence for axon terminal sprouting.

Soussi R, Boulland JL, Bassot E, Bras H, Coulon P, Chaudhry FA, Storm-Mathisen J, Ferhat L, Esclapez M - Brain Struct Funct (2014)

Synaptic targets of ectopic dentate gyrus afferents from SuM neurons in pilocarpine-treated rats. a–h Comparison of distribution patterns of VGLUT2-containing terminals (brown) and NeuN-labeled dentate granule cells (red) in coronal sections of the dorsal DG from a control rat (a, b) and pilocarpine-treated animals at 2 weeks (c, d), 2 months (e, f) and 12 months (g, h). b, d, f, h High magnifications of outlined areas, respectively, illustrated in panels a, c, e and g. In pilocarpine-treated rats (c–h), the distribution pattern of dentate granule cell somata was similar to that observed in the control animal (a, b). No dispersion or bi-lamination of granule cells was associated with the aberrant VGLUT2-immunolabeling observed in the IML in pilocarpine-treated rat from 2 weeks on. i A section of dorsal DG from an epileptic animal at 2 months that was injected into the CA3 stratum lucidum of the dorsal hippocampus with the Rabies virus (RV) retrograde tracer to label cell bodies and dendritic trees of dentate granule cells (G). j–k Image corresponding to a maximum intensity projection of a confocal slice z-stack (20 optical slices, spaced at 296 nm) showing labeling for the RV (green), VGAT (red) and VGLUT2 (blue) in the dorsal dentate gyrus of an epileptic rat at 2 month after pilocarpine injection. j High magnification of the region indicated by an arrow and a star in panel (i). Presumed axon terminals from SuM neurons, labeled for VGAT and VGLUT2, displayed an aberrant distribution with many boutons present in the entire IML including the upper part. Note that in the epileptic rat, the proximal apical dendrites (arrow) of dentate granule cells (*) across the IML displayed a low number of spines as compared to more distal segment. k Higher magnification of the outlined region indicated in panel j showing a dendritic tree of dentate granule cell across the upper IML contacted by ectopic VGLUT2/VGAT-containing axon terminals. l, m Images of the three different fluorophores used for the triple labeling, obtained by sequential acquisitions of separate wavelength channels from a single confocal slice, in the two outlined regions of the IML indicated in panel k and demonstrating that ectopic axon terminals labeled for VGAT (red, arrowhead) and VGLUT2 (blue, arrowhead), presumably originating from the SuM establish contact on the dendritic shafts of dentate granule cells retrogradely labeled with rabies virus (green). Scale bars 200 µm in a, c, e and g; 50 µm in b, d, f and h; 100 µm in i; 15 µm in j; 1 µm in k; 0.5 µm in l, m
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4481331&req=5

Fig7: Synaptic targets of ectopic dentate gyrus afferents from SuM neurons in pilocarpine-treated rats. a–h Comparison of distribution patterns of VGLUT2-containing terminals (brown) and NeuN-labeled dentate granule cells (red) in coronal sections of the dorsal DG from a control rat (a, b) and pilocarpine-treated animals at 2 weeks (c, d), 2 months (e, f) and 12 months (g, h). b, d, f, h High magnifications of outlined areas, respectively, illustrated in panels a, c, e and g. In pilocarpine-treated rats (c–h), the distribution pattern of dentate granule cell somata was similar to that observed in the control animal (a, b). No dispersion or bi-lamination of granule cells was associated with the aberrant VGLUT2-immunolabeling observed in the IML in pilocarpine-treated rat from 2 weeks on. i A section of dorsal DG from an epileptic animal at 2 months that was injected into the CA3 stratum lucidum of the dorsal hippocampus with the Rabies virus (RV) retrograde tracer to label cell bodies and dendritic trees of dentate granule cells (G). j–k Image corresponding to a maximum intensity projection of a confocal slice z-stack (20 optical slices, spaced at 296 nm) showing labeling for the RV (green), VGAT (red) and VGLUT2 (blue) in the dorsal dentate gyrus of an epileptic rat at 2 month after pilocarpine injection. j High magnification of the region indicated by an arrow and a star in panel (i). Presumed axon terminals from SuM neurons, labeled for VGAT and VGLUT2, displayed an aberrant distribution with many boutons present in the entire IML including the upper part. Note that in the epileptic rat, the proximal apical dendrites (arrow) of dentate granule cells (*) across the IML displayed a low number of spines as compared to more distal segment. k Higher magnification of the outlined region indicated in panel j showing a dendritic tree of dentate granule cell across the upper IML contacted by ectopic VGLUT2/VGAT-containing axon terminals. l, m Images of the three different fluorophores used for the triple labeling, obtained by sequential acquisitions of separate wavelength channels from a single confocal slice, in the two outlined regions of the IML indicated in panel k and demonstrating that ectopic axon terminals labeled for VGAT (red, arrowhead) and VGLUT2 (blue, arrowhead), presumably originating from the SuM establish contact on the dendritic shafts of dentate granule cells retrogradely labeled with rabies virus (green). Scale bars 200 µm in a, c, e and g; 50 µm in b, d, f and h; 100 µm in i; 15 µm in j; 1 µm in k; 0.5 µm in l, m
Mentions: The distribution pattern of VGLUT2 immunolabeling associated with that of NeuN-labeled dentate granule cells was analyzed in control (Fig. 7a, b) and pilocarpine-treated animals at 2 weeks (Fig. 7c, d), 2 months (Fig. 7e, f) and 12 months (Fig. 7g, h). No dispersion or bi-laminar organization of dentate granule cells correlated with the aberrant pattern of VGLUT2-containing terminals in the IML of all pilocarpine-treated rats examined (Fig. 7c–h). The thickness of the dentate granule cell layer was relatively similar in control and pilocarpine-treated rats, even though dentate granule cells in pilocarpine-treated animals displayed a decreased labeling intensity for NeuN (Fig. 7c–h) compared to control rats (Fig. 7a, b). Virtually no NeuN-labeled cell body was evident in the IML of pilocarpine-treated animals displaying increased number of VGLUT2-containing terminals at 2 weeks (Fig. 7c, d), 2 months (Fig. 7e, f) and 12 months (Fig. 7g, h) after pilocarpine injection.Fig. 7

Bottom Line: This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE.This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy.It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG.

View Article: PubMed Central - PubMed

Affiliation: INSERM, UMR 1106, Institut de Neurosciences des Systèmes - INS, 13385, Marseille, France.

ABSTRACT
In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate from a multi-structural epileptogenic zone, including several regions of the limbic system connected to the hippocampal formation. In this study, we investigate the structural connectivity between the supramammillary nucleus (SuM) and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the rat. This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents originating from the SuM in pilocarpine-treated rats. This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy. It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG. This reorganization, which reflects an axon terminal sprouting from SuM neurons, could contribute to trigger spontaneous seizures within an altered hippocampal intrinsic circuitry.

No MeSH data available.


Related in: MedlinePlus