Entorhinal cortex of the rat: cytoarchitectonic subdivisions and the origin and distribution of cortical efferents

Hippocampus. 1997;7(2):146-83. doi: 10.1002/(SICI)1098-1063(1997)7:2<146::AID-HIPO4>3.0.CO;2-L.


The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Brain Mapping*
  • Efferent Pathways / physiology
  • Efferent Pathways / ultrastructure
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / physiology*
  • Female
  • Frontal Lobe / physiology
  • Gyrus Cinguli / physiology
  • Image Processing, Computer-Assisted
  • Neurons / physiology*
  • Occipital Lobe / physiology
  • Olfactory Pathways / physiology
  • Parietal Lobe / physiology
  • Prefrontal Cortex / physiology
  • Rats
  • Rats, Wistar
  • Temporal Lobe / physiology