Related Experiment Videos
Connections of the hippocampal formation in humans: I. The mossy fiber pathway
1Committee on Neurobiology, University of Chicago, Illinois 60637, USA.
Insights
This study reveals the human hippocampal mossy fiber pathway, noting minor deviations from rodents but similarities to monkeys. These changes likely reflect the phylogenetic growth of CA3 pyramidal neurons, impacting primate hippocampal function.
Area of Science:
- Neuroscience
- Comparative Anatomy
- Human Anatomy
Background:
- The hippocampal formation is well-studied in rodents, but primate hippocampal anatomy, especially the mossy fiber pathway, remains largely unknown.
- Understanding human hippocampal circuitry is crucial for comparative neuroscience and neurological research.
Purpose of the Study:
- To investigate the anatomical connections of the human hippocampal mossy fiber pathway.
- To compare the human mossy fiber pathway with those in rodents and other primates.
Main Methods:
- Utilized calbindin-D28K antibody staining in normal autopsy tissue.
- Employed neuronal tracers (biocytin, biotinylated dextrans) in in vitro hippocampal slices from epilepsy surgery patients.
- Performed light and electron microscopy on labeled neuronal structures.
Main Results:
- Identified basal dendrites on approximately 30% of human dentate granule cells.
- Described the organization and course of mossy fibers within the human hippocampus, noting rostral prominence.
- Characterized mossy fiber enlargements as synaptic boutons with asymmetric synapses.
- Observed minor deviations from rodent mossy fiber pathways but significant similarities to monkey pathways.
Conclusions:
- Human mossy fiber pathway shows minor differences from rodents, largely mirroring primate evolution.
- Observed anatomical changes are attributed to the phylogenetic expansion of CA3c pyramidal neurons into the hilus.
- This expansion may indicate an increased role for the dentate granule cell to CA3c to CA1 projection in primate hippocampal function.
Abstract:
The hippocampal formation has been one of the most extensively studied cortical regions in rats, yet little is known about the anatomical connections of the hippocampus in primates, especially humans. With the use of an antibody against the calcium-binding protein, calbindin-D28K, in normal autopsy tissue and the neuronal tracers biocytin or biotinylated dextrans in in vitro slice preparations from tissue removed during surgery for intractable epilepsy, we examined the human hippocampal mossy fiber pathway. The injections of biocytin into the dentate granule cell layer labeled neurons in a Golgi-like manner, revealing the presence of basal dendrites on about 30% of the granule cells. The granule cell axons, the mossy fibers, initially formed a diffuse plexus of fibers in the polymorphic layer before organizing into fiber fascicles in the hilar pyramidal region. These fiber fascicles were much more prominent rostrally than caudally. Within the hilus and proximal portions of the extrahilar CA3 field, the mossy fibers ran through the pyramidal cell layer, and while near the transition to field CA2, the fibers turned superficially and crossed the pyramidal layer to run in the stratum lucidum. All of these features, seen following injections of tracer into hippocampal slices from the brains of epileptics, were confirmed by calbindin-staining of mossy fibers in normal brains. Biocytin-labeled mossy fiber axons revealed two characteristic types of enlargements: small varicosities and larger expansions. The expansions were found throughout the neuropil and were highly irregular, diaminobenzidine-dense profiles that had pleiomorphic modes of attachment to the parent axon. Electron microscopic images of these biocytin labeled expansions revealed that they were large synaptic boutons bearing asymmetric synapses. This study indicates that the human mossy fiber pathway shows some minor deviations from the rodent brain but little difference from monkeys. We argue that these changes mirror a phylogenetic growth of the CA3 pyramidal neurons (subfield CA3c) into the hilus rather than an evolutionary change of the mossy fiber pathway. This growth of subfield CA3c and the increase in mossy fibers running through the pyramidal layer (and a presumed accompanying increase in proximal basal dendritic contacts) may reflect a growing role of the projection from the dentate granule cells to subfield CA3c and from there to field CA1 in the primate hippocampus.