The role of the direct perforant path input to the CA1 subregion of the dorsal hippocampus in memory retention and retrieval

Abstract

Subregional analyses of the hippocampus have suggested a selective role for the CA1 subregion in intermediate/long-term spatial memory and consolidation, but not short-term acquisition or encoding processes. It remains unclear how the direct cortical projection to CA1 via the perforant path (pp) contributes to these CA1-dependent processes. It has been suggested that dopamine selectively modulates the pp projection to CA1 while having little to no effect on the Schaffer collateral (SC) projection to CA1. This series of behavioral and electro-physiological experiments takes advantage of this pharmacological dissociation to demonstrate that the direct pp inputs to CA1 are critical in CA1-dependent intermediate-term retention and retrieval function. Here we demonstrate that local infusion of the nonselective dopamine agonist, apomorphine (10, 15 μg), into the CA1 subregion of awake animals produces impairments in between-day retention and retrieval, sparing within-day encoding of a modified Hebb-Williams maze and contextual conditioning of fear. In contrast, apomorphine produces no deficits when infused into the CA3 subregion. To complement the behavioral analyses, electrophysiological data was collected. In anesthetized animals, local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the more proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in the EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a more fundamental role for EC-CA1 synaptic transmission in terms of intermediate-term, but not short-term spatial memory.

Qualitatively Different Hippocampal Subfield Engagement Emerges with Mastery of a Spatial Memory Task by Rats

“…Based on the path analyses, we propose that the CA3 afferents (its temporoammonic path and the Schaffer collaterals) become less influential with additional training, leaving CA1 to be coupled with the medial entorhinal cortex directly via the its own temporoammonic pathway, not the trisynaptic circuit. This view is consistent with the proposed importance of temporoammonic but not trisynaptic circuit inputs to CA1 in the maintenance of spatial representations (Brun et al, 2002), and in the consolidation of intermediate-or long-but not short-term memory (Remondes and Schuman, 2004;Vago et al, 2007). Our findings support the view that, via their physiological differences and their parallel inputs from the entorhinal cortex, hippocampal subfields can contribute to spatial tasks in distinct ways (Lörincz and Buzsáki, 2000;Witter et al, 2000;Brun et al, 2002;.…”

“…The correlational findings fit the general model that the dentate gyrus, and its influence on CA3, is more important for the encoding of spatial information but not necessarily for retrieval processes, whereas CA3 and especially CA1 are more critical for consolidation or retrieval processes (Jarrard et al, 1984;McClelland and Goddard, 1996;Lassalle et al, 2000;Daumas et al, 2005;Rolls and Kesner, 2006;Vago et al, 2007). Although a previous study was able to link zif268 activation in CA1 with context retrieval (Hall et al, 2001), the present study could not test this possibility directly.…”

Brain activation pattern depends on the strategy chosen by zebra finches to solve an orientation task

“…It may nonetheless be possible to speculate about the impact of our results on proposed homologies of avian and mammalian hippocampal subdivisions. For mammals, a widely accepted model relates the dentate gyrus to acquisition of information in learning of spatial tasks, while CA3 and, more especially, CA1 are thought to be involved in the recall of previously learned information (Jarrad et al, 1984;McClelland and Goddard, 1996;Lassalle et al, 2000;Daumas et al, 2005;Rolls and Kesner, 2006;Vago et al, 2007). In birds, there are two contrasting opinions concerning the position of the dentate gyrus within the hippocampal formation.…”

Behavioral functions of the CA3 subregion of the hippocampus

“…The assumption made in this analysis was that the encoding of spatial information predominated during day 1, and retrieval of consolidated spatial information predominated during the first five trials during day 2. The results from testing rats in the Hebb-Williams maze indicate that CA3a,b, but not CA1, lesions impair within-day learning (encoding) and CA1, but not CA3a,b, lesions impair retrieval across days (Jerman et al 2006;Vago et al 2007). Finally, CA3 lesioned rats are impaired in the standard water maze task, which requires multiple trials (Brun et al 2002;Florian and Roullet 2004), although mice that lacked NMDA receptors in CA3 do not appear to be impaired in learning the water maze (Nakazawa et al 2002).…”

“…For example, lesions of the CA3a,b, but not the CA1, subregion impair the acquisition of object-place and odor-place pairedassociate learning (Gilbert and Kesner 2003), and acquisition of the DNMP task on an eight-arm maze with 10-sec delays (Lee and Kesner 2003). Furthermore, CA3a,b, but not CA1, lesions impair within-day learning (encoding) in a Hebb-Williams maze (Jerman et al 2006;Vago et al 2007). Given that CA1 represents the primary output from the hippocampus, especially in light of the fact that CA3a,b does not have direct axonal projections to the subiculum or entorhinal cortex, how can information be transmitted to other neural regions outside the hippocampus once CA1 is ablated?…”