Article thumbnail

Characterization of NMDAR-Independent Learning in the Hippocampus

By Kaycie Kuss Tayler, Elizabeth Lowry, Kazumasa Tanaka, Brynne Levy, Leon Reijmers, Mark Mayford and Brian J. Wiltgen


It is currently thought that memory formation requires the activation of NMDA receptors (NMDARs) in the hippocampus. However, recent studies indicate that these receptors are not necessary for all forms of learning. The current experiments examine this issue using context fear conditioning in mice. First, we show that context fear can be acquired without NMDAR activation in previously trained animals. Mice trained in one environment (context A) are subsequently able to learn about a second environment (context B) in the presence of NMDAR antagonists. Second, we demonstrate that NMDAR-independent learning requires the hippocampus and is dependent on protein synthesis. However, unlike NMDAR-dependent learning, it is not contingent on the expression of activity-regulated cytoskeleton-associated protein (Arc). Lastly, we present data that suggests NMDAR-independent learning is only observed when recently stimulated neurons are reactivated during conditioning. These data suggest that context fear conditioning modifies synaptic plasticity mechanisms in the hippocampus and allows subsequent learning to occur in the absence of NMDAR activation

Topics: Neuroscience
Publisher: Frontiers Research Foundation
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2007). A form of perforant path LTP can occur without ERK1/2 phosphorylation or immediate early gene induction.
  2. (1998). Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats.
  3. Analyzing real-time PCR data by the comparative C(T) method.
  4. (2006). Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.
  5. (2008). D-cycloserine facilitates extinction the first time but not the second time: an examination of the role of NMDA across the course of repeated extinction sessions.
  6. (2004). Differences in hippocampal neuronal population responses to modifications of an environmental context: evidence for distinct, yet complementary, functions of CA3 and CA1 ensembles.
  7. (2000). Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice.
  8. (1999). Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles.
  9. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval.
  10. (2009). Infusion of the NMDA receptor antagonist, DL-APV, into the basolateral amygdala disrupts learning to fear a novel and a familiar context as well as relearning to fear an extinguished context.
  11. (2000). Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.
  12. (2002). Insights into immediate-early gene function in hippocampal memory consolidation using antisense oligonucleotide and fluorescent imaging approaches.
  13. (2001). Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning.
  14. (2007). Localization of a stable neural correlate of associative memory.
  15. (2004). LTP and LTD: an embarrassment of riches.
  16. (1999). Molecular mechanisms of synaptic plasticity and memory.
  17. (2008). Neural mechanisms of extinction learning and retrieval.
  18. (1997). Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats.
  19. (1995). NMDA and non-NMDA receptors contribute to synaptic transmission between the medial geniculate body and the lateral nucleus of the amygdala.
  20. (2003). Pre-training prevents context fear conditioning deficits produced by hippocampal NMDA receptor blockade.
  21. (2008). Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I.
  22. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5.
  23. (2009). Selective survival and maturation of adultborn dentate granule cells expressing the immediate early gene Arc/Arg3.1. PLoS One 4, e4885. doi: 10.1371/journal.pone.0004885 term potentiation.
  24. (1995). Spatial learning without NMDA receptordependent long-term potentiation.
  25. (2009). Storage or retrieval deficit: the yin and yang of amnesia.
  26. (1995). Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo.
  27. (2008). The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear.
  28. (1998). The dorsal hippocampus is essential for context discrimination but not for contextual conditioning.
  29. (1996). The essential role of hippocampal CA1 NMDA receptordependent synaptic plasticity in spatial memory.
  30. (2010). The temporal specificity of the switch from NMDAr-dependent extinction to NMDAr-independent re-extinction.
  31. (2006). Transient incorporation of native