Figure 3.

Lamina-specific axon sprouting and reactive gliosis following perforant path lesion. The molecular layer of the adult dentate gyrus is a highly laminated structure with afferent inputs segregated based on their origin and neurotransmitter phenotype. All afferent axons form either symmetrical or asymmetrical synapses with mature granule cells (black traces) in a lamina-specific manner. Left panel: the inner molecular layer (IML) is occupied by the glutamatergic commissural/associational fibers (C/A) that arise from mossy cells in the ipsi- or contralateral hilus. The middle and outer molecular layer (MML, OML) are occupied predominantly by the glutamatergic perforant path (MPP, LPP), which originates in the ipsilateral entorhinal cortex. In rats (but not in mice), there is also a crossed glutamatergic projection from the contralateral entorhinal cortex (cEC) that terminates in the outermost molecular layer (OML). Cholinergic axons (ACh) from the septal nuclei/diagonal band of Broca are interspersed throughout the molecular layer, as are astrocytes (red) and quiescent microglia (green). Right panel: lesion of the entorhinal cortex (red X, left panel) transects both medial and lateral perforant path, thus eliminating the majority of excitatory input into the dentate gyrus. Degeneration of these axons induces lamina-specific sprouting of the remaining septohippocampal (ACh), commissural/associational (C/A), and crossed entorhino-dentate (cEC) afferents. In the rat, the contralateral entorhino-dentate projection (cEC) partially restores excitatory innervation of the mature granule cells (black trace), however, their dendritic length and complexity are still reduced. The microglia (green) and astrocytes (red) become “activated” following lesion, but this response is limited to the deafferented zone. Note the expansion of the inner molecular layer and shrinkage of the outer layers.