Extrinsic projections from area CA₁ of the rat hippocampus: Olfactory, cortical, subcortical, and bilateral hippocampal formation projections

Abstract

Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca. The septal CA1 injections also label terminal fields in contralateral CA1, and in contralateral subicular, postsubicular, perirhinal, and entorhinal cortices. Injections into the splenial one-third of CA1 label axons and terminals in subiculum, postsubiculum, ventral area infraradiata, and lateral septal nucleus, but they do not label axons and terminals on the contralateral side of the brain. Injections in the temporal one-third of CA1 label axons and terminals in subicular, parasubicular, entorhinal, and infraradiata cortices, anterior olfactory nucleus, olfactory bulb, lateral septal nucleus, nucleus accumbens, amygdala, and hypothalamus. The temporal CA1 injections label no axons on the contralateral side of the brain. These data demonstrate that CA1 has more widespread projections than previously appreciated, and they provide the first clear evidence that CA1 projects to the contralateral cortex and to the ipsilateral olfactory bulb, amygdala, and hypothalamus. The results also demonstrate a heterogeneity in the efferent projections originating in different septotemporal levels of CA1.

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

“…However, retrograde tracing using horse radish peroxidase results in labelling of both the area CA1 and the subiculum (Deacon et al, 1983) which suggests that a direct connection from the area CA1 to the perirhinal cortex exists. In a later study using both anterograde and retrograde tracing, a projection originating the septal region of area CA1 was found to terminate in layer VI of the caudal perirhinal cortex (Van Groen and Wyss, 1990).…”

“…The areas can also be defined based on the connections made with subcortical areas, the entorhinal cortex projects to the dentate gyrus (Wyss, 1981) whereas the perirhinal cortex does not (Insausti et al, 1997;Dolorfo and Amaral, 1998;Witter et al, 1999). In addition, the perirhinal cortex receives a much larger input from area CA1 of the hippocampus compared to the entorhinal cortex (Van Groen and Wyss, 1990). On a cellular level, the presence of large, ''stellate'' cells in layer I of the entorhinal cortex and differences in staining were found between the two areas for parvalbumin, calbindin and zinc (Timm's staining; Insausti et al, 1997;Burwell, 2001;Witter, 2002;Canto et al, 2008).…”

“…3a; Swanson and Cowan, 1977;Wyss, 1981;Kosel et al, 1982Kosel et al, , 1983Deacon et al, 1983;Kö hler, 1988;Van Groen and Wyss, 1990;Insausti et al, 1997;Burwell and Amaral, 1998a,b;Shi and Cassell, 1999;Kloosterman et al, 2003b). Based on anatomical (Witter et al, 2000b;Witter, 2002), electrophysiological (Young et al, 1997;Ivanco and Racine, 2000;Naber et al, 1997Naber et al, , 1999Naber et al, , 2001a and functional evidence (Bussey et al, 2000;Wan et al, 2001;Burwell et al, 2004a,b;Jenkins et al, 2004;Amin et al, 2006;Albasser et al, 2010;Romero-Granados et al, 2010), the hippocampal-parahippocampal region of the brain has been implicated in several aspects of learning and memory.…”

“…As well as the hippocampus forming reciprocal connections with the perirhinal cortex (Swanson and Cowan, 1977;Deacon et al, 1983;Kosel et al, 1983;Van Groen and Wyss, 1990;McIntyre et al, 1996;Kloosterman et al, 2003b), it also shows strong interconnectivity with the entorhinal (Steward, 1976;Steward and Scoville, 1976;Swanson and Cowan, 1977;Swanson et al, 1981;Wyss, 1981;Nojyo, 1993, 1995;Ohara et al, 2009) and postrhinal cortices (Kloosterman et al, 2003b). Many of these projections have been shown to be capable of eliciting an electrophysiological response in their respective tissues.…”

“…Here the perirhinal cortex plays more of an associative role compared to its role in recognition memory (Kholodar-Smith et al, 2008b). Based on the anatomical projections described in Sections 3.2 and 3.3, it is not surprising that the perirhinal cortex is required for such associational learning as it forms a significant reciprocal connections with the amygdala Price, 1974, 1977;Ottersen, 1982;McDonald and Jackson, 1987;Pitkä nen et al, 2000;Pikkarainen and Pitkä nen, 2001;Furtak et al, 2007b), thalamus (Cornwall and Phillipson, 1988;Wouterlood et al, 1990;Shibata, 1993;McIntyre et al, 1996;Van Groen et al, 1999;Vertes et al, 2006), medial prefrontal cortex (Deacon et al, 1983;Sesack et al, 1989;Burwell and Amaral, 1998b;Delatour and Witter, 2002;Heidbreder and Groenewegen, 2003;Jones and Witter, 2007;Agster and Burwell, 2009) and hippocampus (Swanson and Cowan, 1977;Deacon et al, 1983;Kosel et al, 1983;Van Groen and Wyss, 1990;McIntyre et al, 1996;Naber et al, 1999;Shi and Cassell, 1999;Witter et al, 1999;Kloosterman et al, 2003b); regions of the brain which have been strongly linked with fear conditioning (Milad et al, 2006;Rosen and Donley, 2006).…”