Maintenance of peripheral dendrites of GABAergic neurons requires specific input

doi:10.1016/0006-8993(91)90205-A

Brain Research

Volume 554, Issues 1–2, 19 July 1991, Pages 304-307

https://doi.org/10.1016/0006-8993(91)90205-A Get rights and content

This study demonstrates that the removal of a major hippocampal afferent system, the fibers from the entorhinal cortex, results in transneuronal changes in postsynaptic GABAergic inhibitory neurons. Following swelling of their distal segments, the peripheral dendrites of these cells retract from the termination zones of degenerating entorhinal fibers in the outer molecular layer of the fascia dentata and in stratum lacunosum-moleculare of the hippocampus proper. These dendritic alterations are long-lasting and do not seem to be restored by sprouting of other intact afferents. Persisting transneuronal changes in GABAergic hippocampal neurons following the removal of their entorhinal afferents may play a role in Alzheimer's disease since there is a severe degeneration of the entorhino-hippocampal projection in this neurodegenerative disorders.

References (18)

CelioM.R. et al.
Monoclonal antibodies directed against the calcium-binding protein parvalbumin
Cell Calcium
(1988)
KosakaT. et al.
GABAergic neurons containing the Ca²⁺-binding protein parvalbumin in the rat hippocampus and dentate gyrus
Brain Research
(1987)
MatthewsD.A. et al.
An electron microscopic study of lesion induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration
Brain Research
(1976)
MatthewsD.A. et al.
An electron microscopic study of lesion induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts
Brain Research
(1976)
AndersenP. et al.
Lamellar organization of hippocampal excitatory pathways
Exp. Brain Res.
(1971)
CaceresA. et al.
Dendritic reorganization in the denervated dentate gyrus of the rat following entorhinal cortical lesions: a Golgi and electron microscopic analysis
J. Comp. Neurol.
(1983)
CajalS.R.Y.
Degeneration and Regeneration in the Nervous System
(1928)
CelioM.R.
Parvalbumin in most gamma-aminobutyric acid-containing neurons in the cat cerebral cortex
Science
(1986)
CotmanC.W. et al.
Reactive synaptogenesis in the hippocampus

There are more references available in the full text version of this article.

Cited by (47)

Lesion-induced sprouting promotes neurophysiological integration of septal and entorhinal inputs to granule cells in the dentate gyrus of rats
2023, Neurobiology of Learning and Memory
Axonal sprouting of dentate gyrus (DG) afferents after entorhinal cortex (EC) lesion is a model preparation to assess lesion-induced functional reorganization in a denervated target structure. Following a unilateral EC lesion, the surviving contralateral entorhinal projection, termed the crossed temporodentate pathway (CTD), and the heterotypic septal input to the DG, the septodentate pathway (SD), undergo extensive axonal sprouting. We explored whether EC lesion alters the capacity of the SD pathway to influence CTD-evoked granule cell excitability in the DG. We recorded extracellular field excitatory postsynaptic potentials (fEPSPs) after CTD stimulation alone and paired SD-CTD stimulation. Male rats were given unilateral EC lesions or sham operations; evoked fEPSPs in the DG were recorded at 4-, 15-, and 90-days post-entorhinal lesion to assess functional reorganization of the CTD and SD pathways. We found significantly increased fEPSP amplitudes in cases with unilateral lesions compared to sham-operates at 15- and 90-days post lesion. Within each time point, paired SD-CTD stimulation resulted in significantly depressed fEPSP amplitudes compared to amplitudes evoked after CTD stimulation alone and this effect was solely seen in cases with EC lesion. In cases where granule cell discharge was observed, SD stimulation increased discharge amplitude elicited by the CTD stimulation at 90-days postlesion. These findings demonstrate that synaptic remodeling following unilateral cortical lesion results in a synergistic interaction between two established hippocampal afferents that is not seen in uninjured brains. This work may be important for models of neurodegenerative disease and neural injury that target these structures and associated hippocampal circuitry.
Unilateral entorhinal denervation leads to long-lasting dendritic alterations of mouse hippocampal granule cells
2011, Experimental Neurology
Citation Excerpt :
Among the axons that sprout are crossed entorhinal axons which are functionally and structurally homologue to the ipsilateral entorhinal axons (Steward et al., 1973, 1974; Deller et al., 1996). Since maintenance of dendrites in the adult brain requires specific input (Nitsch and Frotscher, 1991), it is conceivable that sprouting of homologue axons could compensate for the loss of innervation and could maintain or even reconstruct the dendritic arbor of denervated neurons (Caceres and Steward, 1983; Steward, 1994). In the mouse dentate gyrus the anatomical situation is different from the rat (Deller et al., 2007), for review).
Following brain injury, neurons efferently connected from the lesion site are denervated and remodel their dendritic tree. Denervation-induced dendritic reorganization of granule cells was investigated in the dentate gyrus of the Thy1-GFP mouse. After mechanical transection of the perforant path, single granule cells were 3D-reconstructed at different time points post-lesion (3 d, 7 d, 10 d, 30 d, 90 d and 180 d) and their soma size, total dendritic length, number of dendritic segments and dendritic branch orders were studied. Changes in spine densities were determined using 3D-analysis of individual dendritic segments. Following entorhinal denervation the granule cell arbor progressively atrophied until 90 d post-lesion (reduction of total dendritic length to ~ 50% of control). Dendritic alterations occurred selectively in the denervated outer molecular layer, where a loss of distal dendritic segments and a reduction of mean segment length were seen. At 180 d post-lesion total dendritic length partially recovered (~ 70% of control). This recovery appeared to be the result of a re-elongation of surviving dendrites rather than dendritic re-branching, since the number of dendritic segments did not recover. In contrast to the protracted dendritic changes, spine density changes followed a faster time course. In the denervated layer spine densities dropped to ~ 65% of control values and fully recovered by 30 d post-lesion. We conclude that entorhinal denervation in mouse causes protracted and long-term structural alterations of the granule cell dendritic tree. Spontaneously occurring reinnervation processes, such as the sprouting of surviving afferent fibers, are insufficient to maintain the granule cell dendritic arbor.
Structural reorganization of the dentate gyrus following entorhinal denervation: species differences between rat and mouse
2007, Progress in Brain Research
Citation Excerpt :
Similar to granule cells, the distal dendrites of parvalbumin-positive neurons demonstrated degenerative changes (Nitsch and Frotscher, 1991, 1992, 1993). These degenerative changes persisted, with only a slight recovery by 2 months postlesion (Nitsch and Frotscher, 1991). In mice, morphological changes of granule cells have not yet been studied at the level of single cells, and at present only indirect — and controversial — data are available.
Deafferentation of the dentate gyrus by unilateral entorhinal cortex lesion or unilateral perforant pathway transection is a classical model to study the response of the central nervous system (CNS) to denervation. This model has been extensively characterized in the rat to clarify mechanisms underlying denervation-induced gliosis, transneuronal degeneration of denervated neurons, and collateral sprouting of surviving axons. As a result, candidate molecules have been identified which could regulate these changes, but a causal link between these molecules and the postlesional changes has not yet been demonstrated. To this end, mutant mice are currently studied by many groups. A tacit assumption is that data from the rat can be generalized to the mouse, and fundamental species differences in hippocampal architecture and the fiber systems involved in sprouting are often ignored. In this review, we will (1) provide an overview of some of the basics and technical aspects of the entorhinal denervation model, (2) identify anatomical species differences between rats and mice and will point out their relevance for the axonal reorganization process, (3) describe glial and local inflammatory changes, (4) consider transneuronal changes of denervated dentate neurons and the potential role of reactive glia in this context, and (5) summarize the differences in the reorganization of the dentate gyrus between the two species. Finally, we will discuss the use of the entorhinal denervation model in mutant mice.
Blockade of neuronal activity alters spine maturation of dentate granule cells but not their dendritic arborization
1999, Neuroscience
Organotypic co-cultures of the entorhinal cortex and hippocampus were examined to determine the role of the entorhinal fibers in the dendritic development and formation of spines of dentate granule cells. Quantitative analysis of Golgi-impregnated granule cells in single hippocampal cultures and co-cultures with the entorhinal cortex revealed that the presence of entorhinal fibers promoted the elongation and differentiation of the target granule cell dendrites. This was accompanied by an increase in the total number of spines. The contribution of neuronal activity to this afferent-mediated dendritic development was tested by chronic application of the sodium channel blocker tetrodotoxin for 20 days in vitro. Tracing with biocytin showed that the formation of the entorhinohippocampal pathway was unaffected by the blockade of neuronal activity. The dendritic arbor of cultured granule cells and the number of dendritic spines did not differ between tetrodotoxin-treated slices and untreated controls. However, there was a significant increase in the relative number of filiform spines on granule cell dendrites in tetrodotoxin-treated co-cultures. Such filiform spines are a characteristic feature of immature neurons.
These results suggest the cooperation of two mechanisms in the dendritic development of dentate granule cells: the specific afferent-mediated dendritic arborization and the activity-dependent maturation of spines.
Differential induction of c-Fos, c-Jun and Jun B in the rat central nervous system following unilateral entorhinal cortex lesion
1999, Neuroscience
In order to identify some of the molecular mechanisms that occur after a central nervous system trauma, the immediate early gene encoded proteins c-Fos, c-Jun and Jun B were analysed by immunocytochemistry following unilateral entorhinal cortex lesion (controls, 30 min, 2, 5, 12 and 24 h, two, six, 10 and 14 days, four weeks and six months postlesion). In the dentate gyrus, c-Fos was induced in some supragranular neurons (30 min), massively expressed in granule cells ipsilaterally to the lesion (2 h), expressed in hilar neurons (5 h and two days) and was absent at all later stages. A basal expression of c-Jun was found in dentate granule cells of controls, which was strongly increased on the lesion side (2 h) and on the side contralateral to the lesion (12 h). c-Jun expression returned to control levels by 24 h. Jun B was induced in granule cells ipsilateral to the lesion within 2 h and was back to control levels by 5 h. In the lateral septal area, c-Fos and c-Jun were induced 30 min postlesion and decreased rapidly thereafter. In the cerebral cortex, a widespread induction of c-Fos and c-Jun occurred within 30 min after entorhinal cortex lesion and this up-regulation lasted until two days postlesion.
These data indicate that electrolytic lesion of the entorhinal cortex leads to a rapid and widespread induction of c-Fos, c-Jun and Jun B. Within the denervated fascia dentata, some of these changes may be linked to the reorganization processes following the lesion. Alternatively, the alterations in immediate early gene expression reported here may to be due to changes in synaptic activity or postlesional seizures which occur in this lesioning paradigm.
Immunohistochemical evidence for dysregulation of the gabaergic system ipsilateral to photochemically induced cortical infarcts in rats
1998, Neuroscience
Deficits of GABAergic transmission have been reported to occur in tissue surrounding ischemic cortical lesions between a few days and several weeks after the insult. In the present experiments, we used immunohistochemistry with antibodies aagainst parvalbumin and two major subunits of the GABA_A receptor (α1, α2) to characterize the events that underlie these changes at different levels of circuit organization. Neocortical infarcts (∼2 mm diameter) consistently affecting medial parts of the primary somatosensory cortex were induced photochemically in adult male Wistar rats; animals were allowed to recover for one week before perfusion–fixation. When compared to controls the pattern of immunoreactivity had changed for the α1 subunit of the GABA_A receptor seven days after the insult. Ipsilateral to the ischemic lesions, we found a decrease in staining intensity reaching up to 4 mm laterally, resulting in a partial or complete absence of the normal laminar staining pattern. No consistent changes were observed for the α2 subunit. Parvalbumin staining revealed pathological alterations in a rim of tissue surrounding the infarct, measuring up to 1 mm from the border of the infarcts. Parvalbumin-positive interneurons in this region showed signs of degeneration; both a reduction of the number of dendrites and, to a lesser extent and only immediately adjacent to the ischemic lesions, a reduction of the number of parvalbumin-positive neurons was readily apparent.
The results provide evidence for both a differential regulation of two GABA_A receptor subunits and degenerative changes of parvalbumin-containing interneurons ipsilateral to cortical infarcts. The relevance of these findings for mechanisms underlying long-term recovery, transient functional deficits and postinfarct seizures warrants further investigation.

View all citing articles on Scopus

View full text

Maintenance of peripheral dendrites of GABAergic neurons requires specific input

Cell Calcium

Brain Research

Brain Research

Brain Research

Lamellar organization of hippocampal excitatory pathways

Exp. Brain Res.

Dendritic reorganization in the denervated dentate gyrus of the rat following entorhinal cortical lesions: a Golgi and electron microscopic analysis

J. Comp. Neurol.

Degeneration and Regeneration in the Nervous System

Parvalbumin in most gamma-aminobutyric acid-containing neurons in the cat cerebral cortex

Science

Reactive synaptogenesis in the hippocampus