Abstract
The hippocampal CA1 field processes spatial information, but the relative importance of intra- vs. extra-hippocampal sources of input into CA1 for spatial behavior is unclear. To characterize the relative roles of these two sources of input, originating in the hippocampal field CA3 and in the medial entorhinal cortex (MEC), we studied effects of discrete neurotoxic lesions of CA3 or MEC on concurrent spatial and nonspatial navigation tasks, and on synaptic transmission in afferents to CA1. Lesions in CA3 or MEC regions that abolished CA3-CA1, or reduced MEC-CA1 synaptic transmission, respectively, impaired spatial navigation and unexpectedly interfered with cue response, suggesting that in certain conditions of training regimen, hippocampal activity may influence behavior otherwise supported by nonhippocampal neural networks. MEC lesions had milder and temporary behavioral effects, but also markedly amplified transmission in the CA3-CA1 pathway. Extensive behavioral training had a similar, but more modest effect on CA3-CA1 transmission. Thus, cortical input to the hippocampus modulates CA1 activity both directly and indirectly, through heterosynaptic interaction, to control information flow in the hippocampal loop. Following damage to hippocampal cortical input, the functional coupling of separate intra- and extra-hippocampal inputs to CA1 involved in normal learning may initiate processes that support recovery of behavioral function. Such a process may explain how CA3 lesions, which do not significantly modify the basic features of CA1 neural activity, nonetheless impair spatial recall, whereas lesions of EC input to CA1, which reduce the spatial selectivity of CA1 firing in foraging rats, have only mild effects on spatial navigation.
Highlights
Multiple studies in rats have shown that the integrity of hippocampal CA1 field activity is necessary for the encoding and long-term storage of spatial information (Auer et al, 1989; Remondes and Schuman, 2004; Lee et al, 2005; Poirier et al, 2008; Song et al, 2009)
The damage did not extend to CA1 or subiculum fields (Figure 2C), a conclusion supported by the finding that synaptic transmission in entorhinal cortex (EC)-CA1 pathway of rats with CA3 lesions was at the same level as in the control group (Figure 2D)
CA3-CA1 synaptic responses were completely abolished throughout the CA1 stratum radiatum in the CA3 lesioned rats proximal CA3CA1: trained control (TC), n = 15 slices; CA3 lesion, n = 7 slices, TC vs. CA3 lesion stimulus-field excitatory post-synaptic potentials (fEPSP) slope response curves: F(1, 21) = 35.62, p < 0.001; distal CA3-CA1: TC, n = 15 slices; CA3 lesion, n = 8 slices; TC vs. CA3 lesion stimulus-fEPSP slope response curves: F(1, 22) = 33.19, p < 0.001
Summary
Multiple studies in rats have shown that the integrity of hippocampal CA1 field activity is necessary for the encoding and long-term storage of spatial information (Auer et al, 1989; Remondes and Schuman, 2004; Lee et al, 2005; Poirier et al, 2008; Song et al, 2009). Recent work has focused on the contributions of CA1 inputs to generating the characteristics of place-selective activity in CA1. Consistent with their putative role in memory, CA1 neurons receive no direct sensory information, but rather highly processed multimodal input from the entorhinal cortex (EC), which sends information directly, through the temporoammonic pathway, and indirectly, through the dentate gyrus (DG)-CA3-CA1 loop (the trisynaptic circuit; Amaral and Witter, 1995; Witter and Amaral, 2004). CA3 lesions do not significantly modify CA1 activity features despite associated impairment in spatial recall (Brun et al, 2002). No recent experiment directly compared the relative contributions of EC and CA3 to memory-based performance
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