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The anatomy of the rat fascia dentata — new vistas
ANNALS Of ANATOMY
The anatomy of the rat fascia dentata - new vistas* Thomas Deller Institute of Anatomy, University of Freiburg, P. 0. Box 111, D-79001 Freiburg, Germany
Summary. The rat fascia dentata is frequently used as a model system to analyze normal as well as pathological processes of the brain. The normal anatomy of the fascia dentata is the basis for a meaningful interpretation of experimentally induced changes in this brain region. Using anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHAL) previously unknown commissural as well as entorhinal fiber systems to the fascia dentata were described. These fiber systems need to be incorporated into current concepts of the hippocampal network since they have profound implications for studies of lesion effects in this brain region. Key words: Layer-specificity - Hippocampus - Anterograde tracing - Commissural projection - Entorhino-hippocampal projection - Entorhinal cortex lesion
Introduction The fascia dentata of the rat hippocampal formation has been intensely studied during the last decades (see Amaral and Witter 1995 for review). Due to its relatively simple cytoarchitecture and the lamination of its afferent fiber systems it has been used as a model system to analyze normal as well as pathological processes of the brain. For example, animal models of temporal lobe epilepsy (e. g., Sloviter 1987), central nervous system trauma (e. g., Steward 1991; Frotscher et al. 1997; Deller and Frotscher 1997), and - to some extend - Alzheimer's disease (e. g., Cotman et al. 1990; Price et al. 1994) have been developed and are based on experimentally induced changes in the morphology of the fascia dentata. It is the precise knowledge of the normal anatomy of the fascia dentata Correspondence to: T. Deller
* Wolfgang-Bargmann-Preis lecture at the 92nd meeting of the Anatomische Gesellschaft in Olsztyn, Poland, May 24-27,1997 Ann Anat (1997) 179: 501-504 © Gustav Fischer Verlag
which is the basis for a meaningful interpretation of these experimental studies. Many of the basic anatomical principles were discovered and meticulously described in the seventies and eighties using classical neuroanatomical techniques (see Amaral and Witter 1995, for review). Figure 1 illustrates the basic anatomy of the fascia dentata. The principal neurons, the dentate granule cells, are arranged in a single cell layer and the major afferent fiber systems terminate in the molecular layer. Entorhinal fibers make up the major extrinsic input to the outer molecular layer and were believed to terminate exclusively within this zone. For this reason, the outer molecular layer has been called the "entorhinal zone" of the fascia dentata. Commissural and associational fibers form the main input to the inner molecular layer and especially the commissural fibers have long been believed to terminate exclusively within this layer of the fascia dentata. Since commissural and associational fibers are intrinsic fiber systems of the hippocampal formation, this zone is frequently called the "hippocampal zone". A sharp border divides the main entorhinal fiber plexus from the main commissurallassociational fiber plexus and is regarded as the major boundary of the fascia dentata. In recent years, new neuroanatomical tracer substances were developed and these tools reached an anatomical resolution which could not be achieved with any of the classical techniques. For example, the anterograde tracer Phaseolus vulgaris-Ieucoagglutinin (PHAL; Gerfen and Sawchenko, 1984) which was also used in the studies reported here, allows for the identification of projections at the level of single axons. With the help of these sensitive anterograde tracers the normal anatomy of the fascia dentata was reinvestigated and new aspects of hippocampal topography and connectivity were revealed (e. g., Amaral and Witter 1995). We ourselves could demonstrate previously unknown commissural (Deller et al. 1995 a, 1996 b) as well as entorhinal (Deller et al. 1996 c) projection systems. These systems need to be incorpo-
LAYERS OF THE RAT FASCIA DENTATA
OML
EC
IML
CIA
layer, and hilus of the fascia dentata. Electron microscopy in combination with GABA postembedding immunocytochemistry demonstrated that these entorhinal fibers do indeed form synapses. All synapses which were investigated were of the asymmetric type and none of the entorhinal fibers to the inner molecular layer, granule cell layer, and hilus contained immunolabeling for GABA. Some entorhinal fibers contacted GABA-positive dendrites. Thus, it is very likely that this entorhinal projection is an excitatory glutamatergic projection, similar to the classical entorhinal projection which is restricted to the outer molecular layer of the fascia dentata.
Previously unknown commissural fibers to the outer molecular layer of the fascia dentata
GCL
H
Fig. 1. Lamina-specific termination of entorhinal and commissural fibers to the rat fascia dentata. A typical granule cell of the fascia dentata is illustrated in this schematic diagram (adapted from Zafirov et al. 1994). Entorhinal and commissural fibers terminate on the dendritic arbor of this cell in a lamina-specific fashion. The outer molecular layer (OML) is occupied by fibers of the entorhinal cortex (EC). The inner molecular layer (IML) is occupied by commissural and associational fibers (CIA). GCL - granule cell layer; H - hilus.
rated into contemporary concepts of the hippocampal network since they may have profound implications for animal models investigating changes in the fascia dentata.
Previously unknown entorhinal fibers to the inner molecular layer, granule cell layer, and hilus of the fascia dentata The entorhinal projection to the fascia dentata was analyzed using anterograde tracing with PHAL (Deller et al. 1996 c). Injections into the superficial layers of the entorhinal cortex resulted in the visualization of the classical entorhinal projection to the fascia dentata (see Amaral and Witter 1995 for review). These fibers terminate in a layer-specific fashion in the outer molecular layer. However, after PHAL injections into the deeper layers of the entorhinal cortex, entorhinal fibers that leave the "entorhinal zone" of the fascia dentata were observed. These fibers form numerous boutons in the outer molecular layer, inner molecular layer, granule cell
A very similar situation exists for the commissural projection to the fascia dentata as was demonstrated with PHAL-tracing of the commissural fibers (Deller et al. 1995 a, 1996 b). As reported by earlier investigators (Blackstad 1956; see Amaral and Witter 1995, for review), the majority of commissural fibers was found in the inner molecular layer of the fascia dentata. However, some commissural fibers were observed which did not terminate in the "hippocampal zone" of the dentate. These fibers traverse the inner molecular layer of the fascia dentata without branching and arborize in the outer molecular layer. Electron microscopy in combination with GABA postembedding immunocytochemistry revealed that the commissural fibers to the outer molecular layer form synapses and are GABAergic (Deller et al. 1995).
Implications for animal models of disease The functional relevance of these two previously unknown fiber systems to the fascia dentata needs to be determined and is difficult to estimate presently. It is necessary, however, to consider these projection systems in animal models of disease which have been developed for the fascia dentata. The sprouting of commissural fibers to the fascia dentata after unilateral entorhinal cortex lesion is a good example in this respect. This lesion paradigm is a well established model system to analyze sprouting and neuronal plasticity in the brain (e. g., Steward 1991; Frotscher et al. 1997; Deller and Frotscher 1997). In short, it is based on the removal of the entorhinal input to the fascia dentata and the sprouting of surviving afferent fiber systems which reinnervate the fascia dentata. In this model system, commissural boutons were found in the entorhinal zone of the fascia dentata and because it was believed that no commissural fibers are normally present there - it was assumed that commissur-
502
al fibers invade the denervated outer molecular layer (e. g., Cotman and Nadler 1978). Commissural fibers were believed to grow into the entorhinal zone in a "translaminar sprouting response". In the light of the previously unknown commissural projection to the outer molecular layer of the fascia dentata, a different interpretation of the commissural sprouting response appears to be more likely: Commissural boutons in the outer molecular layer may be explained by the layer-specific sprouting of commissural fibers to the outer molecular layer, i. e., the fibers which normally terminate in the denervated outer molecular layer (Deller et al. 1995 b, 1996 a). Thus, commissural sprouting appears to be the consequence of the layer-specific sprouting of a previously unknown commis-
THE RAT FASCIA DENTATA E TORR
OML
L
COMMISSU
L
-
sural projection in response to lesion rather than the translaminar sprouting response of commissural fibers from the inner molecular layer (Frotscher et al. 1997).
The laminar organization of the rat fascia dentata The use of the sensitive anterograde tracer PHAL to analyze the entorhino-dentate and commissural projections to the rat fascia dentata has confirmed the results of earlier investigators and has revealed new aspects of the laminar organization of the fascia dentata (Fig. 2). First, the majority of entorhinal and commissural fibers terminate in the outer and inner molecular layer, respectively. Second, a weak entorhinal projection exists, which originates from the deep layers of the entorhinal cortex and terminates throughout all layers of the fascia dentata, including the "hippocampal zone". Third, a weak commissural projection exists, which terminates in the outer molecular layer, i. e. the "entorhinal zone". These normal projection systems have to be taken into account in animal models of disease whenever experimentally induced changes in the normal anatomy of the fascia dentata are analyzed and int~rpreted. Acknowledgements. The author thanks Prof. M. Frotscher for reading the manuscript and for his continuous support. Some of the studies reviewed here were part of a collaboration with Prof. R. Nitsch, Charite, Berlin. Dr. A. Martinez was involved in some of the experiments. The expert technical assistance of A. Schneider, R. Hertweck, and M. Winter is gratefully acknowledged. This work was supported by the Deutsche Forschungsgemeinschaft (De 551/5-1, Fr 620/4-2, SFB 505, and Leibniz Programm).
IML
GeL t--
References
H Fig. 2. Synopsis of the entorhinal and commissural fiber systems to the rat fascia dentata with regard to the · main termination zones of the entorhinal and commissural projections. On the left hand side, the normal termination of entorhinal fibers to the rat fascia dentata is illustrated. Shaded in grey is the main termination zone of entorhinal fibers in the outer molecular layer (OML). These fibers originate from the superficial layers of the entorhinal cortex. Entorhinal fibers originating from deeper layers of the entorhinal cortex terminate throughout all layers. On the right hand side, the normal termination of commissural fibers to the rat fascia dentata is illustrated. Shaded in grey is the main termination zone of commissural fibers in the inner molecular layer (IML). Some commissural fibers terminate in the outer molecular layer of the fascia dentata. Thus, weak entorhinal as well as commissural fiber systems exist which do not respect the "classical" laminar boundaries of the fascia dentata. GCL - granule cell layer; H - hilus.
Amaral DG, Witter MP (1995) The hippocampal formation. In: Paximos G (ed) The rat nervous system, 2nd. Academic Press, San Diego, New York, Boston, London, Sydney, Tokyo, Toronto, pp 443-494 Blackstad TW (1956) Commissural connections of the hippocampal region of the rat, with special reference to their mode of termination. J Comp Neurol105: 417-537 Cotman CW, Geddes JW, Kahle JS (1990) Axon sprouting in the rodent and Alzheimer's disease brain: a reactivation of developmental mechanisms? In: Storm-Mathisen J, Zimmer J, Ottersen OP (eds) Understanding the brain through the hippocampus. The hippocampal region as a model for studying brain structure and function. Elsevier Science Publishers B. v., Amsterdam, Prog Brain Res 83: 427-434 Cotman CW, Nadler JV (1978) Reactive synaptogenesis in the hippocampus. In: Cotman CW (ed) Neuronal Plasticity. Raven Press, New York, pp 227-271 Deller T, Nitsch R, Frotscher M (1995 a) Phaseolus vulgaris-leucoagglutinin (PHAL) tracing of commissural fibers to the rat
503
fascia dentata: Evidence for a previously unknown commissural projection to the outer molecular layer. J Comp Neurol 352: 55-68 Deller T, Frotscher M, Nitsch R (1995 b) Morphological evidence for the sprouting of inhibitory commissural fibers in response to the lesion of the excitatory entorhinal input to the rat dentate gyrus. J Neurosci 15: 6868-6878 Deller T, Nitsch R, Frotscher M (1996 a) Layer-specific sprouting of commissural fibers to the rat fascia dentata after unilateral entorhinal cortex lesion: A Phaseolus vulgaris-leucoagglutinin tracing study. Neuroscience 71: 651-660 Deller T, Nitsch R, Frotscher M (1996 b) Heterogeneity of the commissural projection to the rat dentate gyrus: A Phaseolus vulgaris-Leucoagglutinin tracing study. Neuroscience 75: 111121 Deller T, Martinez A , Nitsch R, Frotscher M (1996c) A novel entorhinal projection to the rat dentate gyrus: Direct innervation of proximal dendrites and granule cell bodies of granule cells and GABAergic neurons. J Neuroscience 16: 3322-3333 Deller T, Frotscher M (1997) Lesion-induced plasticity of central neurons: Sprouting of single fibers in the rat hippocampus after unilateral entorhinallesion. Prog Neurobiol, in press.
Frotscher M, Heimrich B, Deller T (1997) Sprouting in the hippocampus is layer specific. Trends Neurosci 20: 218-223 Gerfen CR, Sawchenko PE (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHAL). Brain Res 290: 219-238 Moore RY, Zigmond MJ (1994) Compensatory mechanisms in central neurodegenerative disease. In: Neurodegenerative Diseases (Caine DB, ed). Saunders, Philadelphia, pp 355-370 Price DE, Koliatsos VB, Kitt CE, Walker LC, Cork LC (1994) Animal models of neurodegenerative disease. In: Caine DB (ed), Neurodegenerative Diseases. Saunders, Philadelphia, pp 371-380 Sloviter RS (1987) Decreased hippocampal inhibition and a selective loss of intemeurons in experimental epilepsy. Science 235: 73-76 Steward 0 (1991) Synapse replacement on cortical neurons following denervation. Cerebral Cortex 9: 81-132 Zafirov S, Heimrich B, Frotscher M (1994) Dendritic development of dentate granule cells in the absence of their specific extrinsic afferents. J Comp Neurol 345: 472-480
504
The anatomy of the rat fascia dentata - new vistas* Thomas Deller Institute of Anatomy, University of Freiburg, P. 0. Box 111, D-79001 Freiburg, Germany
Summary. The rat fascia dentata is frequently used as a model system to analyze normal as well as pathological processes of the brain. The normal anatomy of the fascia dentata is the basis for a meaningful interpretation of experimentally induced changes in this brain region. Using anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHAL) previously unknown commissural as well as entorhinal fiber systems to the fascia dentata were described. These fiber systems need to be incorporated into current concepts of the hippocampal network since they have profound implications for studies of lesion effects in this brain region. Key words: Layer-specificity - Hippocampus - Anterograde tracing - Commissural projection - Entorhino-hippocampal projection - Entorhinal cortex lesion
Introduction The fascia dentata of the rat hippocampal formation has been intensely studied during the last decades (see Amaral and Witter 1995 for review). Due to its relatively simple cytoarchitecture and the lamination of its afferent fiber systems it has been used as a model system to analyze normal as well as pathological processes of the brain. For example, animal models of temporal lobe epilepsy (e. g., Sloviter 1987), central nervous system trauma (e. g., Steward 1991; Frotscher et al. 1997; Deller and Frotscher 1997), and - to some extend - Alzheimer's disease (e. g., Cotman et al. 1990; Price et al. 1994) have been developed and are based on experimentally induced changes in the morphology of the fascia dentata. It is the precise knowledge of the normal anatomy of the fascia dentata Correspondence to: T. Deller
* Wolfgang-Bargmann-Preis lecture at the 92nd meeting of the Anatomische Gesellschaft in Olsztyn, Poland, May 24-27,1997 Ann Anat (1997) 179: 501-504 © Gustav Fischer Verlag
which is the basis for a meaningful interpretation of these experimental studies. Many of the basic anatomical principles were discovered and meticulously described in the seventies and eighties using classical neuroanatomical techniques (see Amaral and Witter 1995, for review). Figure 1 illustrates the basic anatomy of the fascia dentata. The principal neurons, the dentate granule cells, are arranged in a single cell layer and the major afferent fiber systems terminate in the molecular layer. Entorhinal fibers make up the major extrinsic input to the outer molecular layer and were believed to terminate exclusively within this zone. For this reason, the outer molecular layer has been called the "entorhinal zone" of the fascia dentata. Commissural and associational fibers form the main input to the inner molecular layer and especially the commissural fibers have long been believed to terminate exclusively within this layer of the fascia dentata. Since commissural and associational fibers are intrinsic fiber systems of the hippocampal formation, this zone is frequently called the "hippocampal zone". A sharp border divides the main entorhinal fiber plexus from the main commissurallassociational fiber plexus and is regarded as the major boundary of the fascia dentata. In recent years, new neuroanatomical tracer substances were developed and these tools reached an anatomical resolution which could not be achieved with any of the classical techniques. For example, the anterograde tracer Phaseolus vulgaris-Ieucoagglutinin (PHAL; Gerfen and Sawchenko, 1984) which was also used in the studies reported here, allows for the identification of projections at the level of single axons. With the help of these sensitive anterograde tracers the normal anatomy of the fascia dentata was reinvestigated and new aspects of hippocampal topography and connectivity were revealed (e. g., Amaral and Witter 1995). We ourselves could demonstrate previously unknown commissural (Deller et al. 1995 a, 1996 b) as well as entorhinal (Deller et al. 1996 c) projection systems. These systems need to be incorpo-
LAYERS OF THE RAT FASCIA DENTATA
OML
EC
IML
CIA
layer, and hilus of the fascia dentata. Electron microscopy in combination with GABA postembedding immunocytochemistry demonstrated that these entorhinal fibers do indeed form synapses. All synapses which were investigated were of the asymmetric type and none of the entorhinal fibers to the inner molecular layer, granule cell layer, and hilus contained immunolabeling for GABA. Some entorhinal fibers contacted GABA-positive dendrites. Thus, it is very likely that this entorhinal projection is an excitatory glutamatergic projection, similar to the classical entorhinal projection which is restricted to the outer molecular layer of the fascia dentata.
Previously unknown commissural fibers to the outer molecular layer of the fascia dentata
GCL
H
Fig. 1. Lamina-specific termination of entorhinal and commissural fibers to the rat fascia dentata. A typical granule cell of the fascia dentata is illustrated in this schematic diagram (adapted from Zafirov et al. 1994). Entorhinal and commissural fibers terminate on the dendritic arbor of this cell in a lamina-specific fashion. The outer molecular layer (OML) is occupied by fibers of the entorhinal cortex (EC). The inner molecular layer (IML) is occupied by commissural and associational fibers (CIA). GCL - granule cell layer; H - hilus.
rated into contemporary concepts of the hippocampal network since they may have profound implications for animal models investigating changes in the fascia dentata.
Previously unknown entorhinal fibers to the inner molecular layer, granule cell layer, and hilus of the fascia dentata The entorhinal projection to the fascia dentata was analyzed using anterograde tracing with PHAL (Deller et al. 1996 c). Injections into the superficial layers of the entorhinal cortex resulted in the visualization of the classical entorhinal projection to the fascia dentata (see Amaral and Witter 1995 for review). These fibers terminate in a layer-specific fashion in the outer molecular layer. However, after PHAL injections into the deeper layers of the entorhinal cortex, entorhinal fibers that leave the "entorhinal zone" of the fascia dentata were observed. These fibers form numerous boutons in the outer molecular layer, inner molecular layer, granule cell
A very similar situation exists for the commissural projection to the fascia dentata as was demonstrated with PHAL-tracing of the commissural fibers (Deller et al. 1995 a, 1996 b). As reported by earlier investigators (Blackstad 1956; see Amaral and Witter 1995, for review), the majority of commissural fibers was found in the inner molecular layer of the fascia dentata. However, some commissural fibers were observed which did not terminate in the "hippocampal zone" of the dentate. These fibers traverse the inner molecular layer of the fascia dentata without branching and arborize in the outer molecular layer. Electron microscopy in combination with GABA postembedding immunocytochemistry revealed that the commissural fibers to the outer molecular layer form synapses and are GABAergic (Deller et al. 1995).
Implications for animal models of disease The functional relevance of these two previously unknown fiber systems to the fascia dentata needs to be determined and is difficult to estimate presently. It is necessary, however, to consider these projection systems in animal models of disease which have been developed for the fascia dentata. The sprouting of commissural fibers to the fascia dentata after unilateral entorhinal cortex lesion is a good example in this respect. This lesion paradigm is a well established model system to analyze sprouting and neuronal plasticity in the brain (e. g., Steward 1991; Frotscher et al. 1997; Deller and Frotscher 1997). In short, it is based on the removal of the entorhinal input to the fascia dentata and the sprouting of surviving afferent fiber systems which reinnervate the fascia dentata. In this model system, commissural boutons were found in the entorhinal zone of the fascia dentata and because it was believed that no commissural fibers are normally present there - it was assumed that commissur-
502
al fibers invade the denervated outer molecular layer (e. g., Cotman and Nadler 1978). Commissural fibers were believed to grow into the entorhinal zone in a "translaminar sprouting response". In the light of the previously unknown commissural projection to the outer molecular layer of the fascia dentata, a different interpretation of the commissural sprouting response appears to be more likely: Commissural boutons in the outer molecular layer may be explained by the layer-specific sprouting of commissural fibers to the outer molecular layer, i. e., the fibers which normally terminate in the denervated outer molecular layer (Deller et al. 1995 b, 1996 a). Thus, commissural sprouting appears to be the consequence of the layer-specific sprouting of a previously unknown commis-
THE RAT FASCIA DENTATA E TORR
OML
L
COMMISSU
L
-
sural projection in response to lesion rather than the translaminar sprouting response of commissural fibers from the inner molecular layer (Frotscher et al. 1997).
The laminar organization of the rat fascia dentata The use of the sensitive anterograde tracer PHAL to analyze the entorhino-dentate and commissural projections to the rat fascia dentata has confirmed the results of earlier investigators and has revealed new aspects of the laminar organization of the fascia dentata (Fig. 2). First, the majority of entorhinal and commissural fibers terminate in the outer and inner molecular layer, respectively. Second, a weak entorhinal projection exists, which originates from the deep layers of the entorhinal cortex and terminates throughout all layers of the fascia dentata, including the "hippocampal zone". Third, a weak commissural projection exists, which terminates in the outer molecular layer, i. e. the "entorhinal zone". These normal projection systems have to be taken into account in animal models of disease whenever experimentally induced changes in the normal anatomy of the fascia dentata are analyzed and int~rpreted. Acknowledgements. The author thanks Prof. M. Frotscher for reading the manuscript and for his continuous support. Some of the studies reviewed here were part of a collaboration with Prof. R. Nitsch, Charite, Berlin. Dr. A. Martinez was involved in some of the experiments. The expert technical assistance of A. Schneider, R. Hertweck, and M. Winter is gratefully acknowledged. This work was supported by the Deutsche Forschungsgemeinschaft (De 551/5-1, Fr 620/4-2, SFB 505, and Leibniz Programm).
IML
GeL t--
References
H Fig. 2. Synopsis of the entorhinal and commissural fiber systems to the rat fascia dentata with regard to the · main termination zones of the entorhinal and commissural projections. On the left hand side, the normal termination of entorhinal fibers to the rat fascia dentata is illustrated. Shaded in grey is the main termination zone of entorhinal fibers in the outer molecular layer (OML). These fibers originate from the superficial layers of the entorhinal cortex. Entorhinal fibers originating from deeper layers of the entorhinal cortex terminate throughout all layers. On the right hand side, the normal termination of commissural fibers to the rat fascia dentata is illustrated. Shaded in grey is the main termination zone of commissural fibers in the inner molecular layer (IML). Some commissural fibers terminate in the outer molecular layer of the fascia dentata. Thus, weak entorhinal as well as commissural fiber systems exist which do not respect the "classical" laminar boundaries of the fascia dentata. GCL - granule cell layer; H - hilus.
Amaral DG, Witter MP (1995) The hippocampal formation. In: Paximos G (ed) The rat nervous system, 2nd. Academic Press, San Diego, New York, Boston, London, Sydney, Tokyo, Toronto, pp 443-494 Blackstad TW (1956) Commissural connections of the hippocampal region of the rat, with special reference to their mode of termination. J Comp Neurol105: 417-537 Cotman CW, Geddes JW, Kahle JS (1990) Axon sprouting in the rodent and Alzheimer's disease brain: a reactivation of developmental mechanisms? In: Storm-Mathisen J, Zimmer J, Ottersen OP (eds) Understanding the brain through the hippocampus. The hippocampal region as a model for studying brain structure and function. Elsevier Science Publishers B. v., Amsterdam, Prog Brain Res 83: 427-434 Cotman CW, Nadler JV (1978) Reactive synaptogenesis in the hippocampus. In: Cotman CW (ed) Neuronal Plasticity. Raven Press, New York, pp 227-271 Deller T, Nitsch R, Frotscher M (1995 a) Phaseolus vulgaris-leucoagglutinin (PHAL) tracing of commissural fibers to the rat
503
fascia dentata: Evidence for a previously unknown commissural projection to the outer molecular layer. J Comp Neurol 352: 55-68 Deller T, Frotscher M, Nitsch R (1995 b) Morphological evidence for the sprouting of inhibitory commissural fibers in response to the lesion of the excitatory entorhinal input to the rat dentate gyrus. J Neurosci 15: 6868-6878 Deller T, Nitsch R, Frotscher M (1996 a) Layer-specific sprouting of commissural fibers to the rat fascia dentata after unilateral entorhinal cortex lesion: A Phaseolus vulgaris-leucoagglutinin tracing study. Neuroscience 71: 651-660 Deller T, Nitsch R, Frotscher M (1996 b) Heterogeneity of the commissural projection to the rat dentate gyrus: A Phaseolus vulgaris-Leucoagglutinin tracing study. Neuroscience 75: 111121 Deller T, Martinez A , Nitsch R, Frotscher M (1996c) A novel entorhinal projection to the rat dentate gyrus: Direct innervation of proximal dendrites and granule cell bodies of granule cells and GABAergic neurons. J Neuroscience 16: 3322-3333 Deller T, Frotscher M (1997) Lesion-induced plasticity of central neurons: Sprouting of single fibers in the rat hippocampus after unilateral entorhinallesion. Prog Neurobiol, in press.
Frotscher M, Heimrich B, Deller T (1997) Sprouting in the hippocampus is layer specific. Trends Neurosci 20: 218-223 Gerfen CR, Sawchenko PE (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHAL). Brain Res 290: 219-238 Moore RY, Zigmond MJ (1994) Compensatory mechanisms in central neurodegenerative disease. In: Neurodegenerative Diseases (Caine DB, ed). Saunders, Philadelphia, pp 355-370 Price DE, Koliatsos VB, Kitt CE, Walker LC, Cork LC (1994) Animal models of neurodegenerative disease. In: Caine DB (ed), Neurodegenerative Diseases. Saunders, Philadelphia, pp 371-380 Sloviter RS (1987) Decreased hippocampal inhibition and a selective loss of intemeurons in experimental epilepsy. Science 235: 73-76 Steward 0 (1991) Synapse replacement on cortical neurons following denervation. Cerebral Cortex 9: 81-132 Zafirov S, Heimrich B, Frotscher M (1994) Dendritic development of dentate granule cells in the absence of their specific extrinsic afferents. J Comp Neurol 345: 472-480
504