A dialogue between the hippocampus and the neocortex is thought to underlie the formation, consolidation and retrieval of episodic memories1,2,3,4, although the nature of this cortico-hippocampal communication is poorly understood. Using selective electrolytic lesions in rats, here we examined the role of the direct entorhinal projection (temporoammonic, TA) to the hippocampal area CA1 in short-term (24 hours) and long-term (four weeks) spatial memory in the Morris water maze. When short-term memory was examined, both sham- and TA-lesioned animals showed a significant preference for the target quadrant. When re-tested four weeks later, sham-lesioned animals exhibited long-term memory; in contrast, the TA-lesioned animals no longer showed target quadrant preference. Many long-lasting memories require a process called consolidation, which involves the exchange of information between the cortex and hippocampus3,5,6. The disruption of long-term memory by the TA lesion could reflect a requirement for TA input during either the acquisition or consolidation of long-term memory. To distinguish between these possibilities, we trained animals, verified their spatial memory 24 hours later, and then subjected trained animals to TA lesions. TA-lesioned animals still exhibited a deficit in long-term memory, indicating a disruption of consolidation. Animals in which the TA lesion was delayed by three weeks, however, showed a significant preference for the target quadrant, indicating that the memory had already been adequately consolidated at the time of the delayed lesion. These results indicate that, after learning, ongoing cortical input conveyed by the TA path is required to consolidate long-term spatial memory.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O'Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683 (1982)
Eichenbaum, H. A cortical-hippocampal system for declarative memory. Nature Rev. Neurosci. 1, 41–50 (2001)
Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neuropsychiatry Clin. Neurosci. 12, 103–113 (1957)
Squire, L. R. & Zola, S. M. Amnesia, memory and brain systems. Phil. Trans. R. Soc. Lond. B 352, 1663–1673 (1997)
McGaugh, J. L. Time-dependent processes in memory storage. Science 153, 1351–1358 (1966)
Squire, L. R. & Alvarez, P. Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr. Opin. Neurobiol. 5, 169–177 (1995)
Skelton, R. W. & McNamara, R. K. Bilateral knife cuts to the perforant path disrupt spatial learning in the Morris water maze. Hippocampus 2, 73–80 (1992)
Eichenbaum, H., Stewart, C. & Morris, R. G. M. Hippocampal representation in place learning. J. Neurosci. 10, 3531–3542 (1990)
Sutherland, R. J., Whishaw, I. Q. & Kolb, B. A behavioural analysis of spatial localization following electrolytic, kainate- or colchicine-induced damage to the hippocampal formation in the rat. Behav. Brain Res. 7, 133–153 (1983)
McNaughton, B. L., Barnes, C. A., Meltzer, J. & Sutherland, R. J. Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Exp. Brain Res. 76, 485–496 (1989)
Jarrard, L. E. Selective hippocampal lesions and behaviour: effects of kainic acid lesions on performance of place and cue tasks. Behav. Neurosci. 97, 873–889 (1983)
Brun, V. H. et al. Place cells and place recognition maintained by the direct entorhinal-hippocampal circuitry. Science 296, 2243–2246 (2002)
Nakazawa, K. et al. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297, 211–218 (2002)
Colbert, C. M. & Levy, W. B. Long-term potentiation of perforant path synapses in hippocampal CA1 in vitro. Brain Res. 606, 87–91 (1993)
Remondes, M. & Schuman, E. M. Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons. Nature 416, 736–740 (2002)
Remondes, M. & Schuman, E. M. Properties of early- and late-phase LTP at temporoammonic-CA1 synapses. Learning Memory 10, 247–252 (2003)
Dvorak-Carbone, H. & Schuman, E. M. Patterned activity in stratum lacunosum moleculare inhibits CA1 pyramidal neuron firing. J. Neurophys. 82, 3213–3222 (1999)
Dvorak-Carbone, H. & Schuman, E. M. Long-term depression of temporoammonic-CA1 hippocampal synaptic transmission. J. Neurophys. 81, 1036–1044 (1999)
Otmakhova, N. A. & Lisman, J. E. Dopamine selectively inhibits the direct cortical pathway to the CA1 hippocampal region. J. Neurosci. 19, 1437–1445 (1999)
El-Ghundi, M. et al. Spatial learning deficit in dopamine D1 receptor knockout mice. Eur. J. Pharmacol. 383, 95–106 (1999)
Li, S., Cullen, W. K., Anwyl, R. & Rowan, M. J. Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nature Neurosci. 6, 526–531 (2003)
Riedel, G. et al. Reversible neural inactivation reveals hippocampal participation in several memory process. Nature Neurosci. 2, 898–905 (1999)
Frankland, P. W., O'Brien, C. O., Ohno, M., Kirkwood, A. & Silva, A. J. Alpha-CAMKII-dependent plasticity in the cortex is required for permanent memory. Nature 411, 309–313 (2001)
Siapas, A. G. & Wilson, M. A. Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep. Neuron 21, 1123–1128 (1998)
Sirota, A., Csicsvari, J., Bhul, D. & Buzsaki, G. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl Acad. Sci. USA 100, 2065–2069 (2003)
Wilson, M. A. & McNaughton, B. L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994)
Lee, A. K. & Wilson, M. A. Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36, 1183–1194 (2002)
We thank T. Siapas, G. Laurent, M. Sutton and other members of the Schuman laboratory for discussions. This work was supported by the Fundacao para a Ciencia e Technologia (FCT)—Portugal and the Howard Hughes Medical Institute.
The authors declare that they have no competing financial interests.
Lesion data for animals included in the behavioural analyses shown in Figures 2 and 3. (JPG 97 kb)
More TA lesion data for all animals included in the behavioural analyses. (JPG 117 kb)
Visible platform data for all animals in all experiments. In addition, probe trial data for animals that received complete hippocampal lesions, and the sham and TA-lesioned animals probe trial at 24 hrs post-training. (JPG 110 kb)
Methods used for surgical procedures, lesion execution and assessment and electrophysiology. (PDF 13 kb)
About this article
NGL-1/LRRC4C Deletion Moderately Suppresses Hippocampal Excitatory Synapse Development and Function in an Input-Independent Manner
Frontiers in Molecular Neuroscience (2019)
Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease
Neurochemical Research (2019)
Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment
Human Brain Mapping (2019)
Combined use of vitamin E and nimodipine ameliorates dibutyl phthalate-induced memory deficit and apoptosis in mice by inhibiting the ERK 1/2 pathway
Toxicology and Applied Pharmacology (2019)