NMDA receptors in mouse anterior piriform cortex initialize early odor preference learning and L-type calcium channels engage for long-term memory.

Bandhan Mukherjee,Qi Yuan

doi:10.1038/srep35256

Abstract

The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV. In mice that underwent early odor preference training, blocking NMDARs in the aPC prevented short-term (3 hr) and long-term (24 hr) odor preference memory, and both memories were rescued when BayK-8644 (LTCC agonist) was co-infused. However, activating LTCCs in the absence of NMDARs resulted in loss of discrimination between the conditioned odor and a similar odor mixture at 3 hr. Elevated synaptic AMPAR expression at 3 hr was prevented by D-APV infusion but restored when LTCCs were directly activated, mirroring the behavioral outcomes. Blocking LTCCs prevented 24 hr memory and spared 3 hr memory. These results suggest that NMDARs mediate stimulus-specific encoding of odor memory while LTCCs mediate intracellular signaling leading to long-term memory.

Highlights

Both NMDA receptors (NMDARs) and L-type calcium channels (LTCCs) are implicated in various learning models such as spatial memory[28,29], fear conditioning[22] and associative olfactory learning[11,27]
In this study we first investigated the relationship of the NMDARs and LTCCs in generating somatic calcium transients in anterior piriform cortex (aPC) pyramidal neurons, and we studied the interaction of the NMDARs and LTCCs in odor preference learning in week-old neonatal mice
We studied the effects of LTCC or NMDAR blockade on somatic calcium transient evoked by lateral olfactory tract (LOT) stimulation

Summary

Introduction

Both NMDARs and LTCCs are implicated in various learning models such as spatial memory[28,29], fear conditioning[22] and associative olfactory learning[11,27]. Odor preference learning can be induced in neonatal rat[30,31] or mouse[32,33] by pairing a novel odor with a tactile stimulus that signals maternal care (e.g. stroking the body of the pup with a brush). This model has the advantage of being well-defined with respect to the sites of learning and the temporal phases of the memory (short-term memory (STM) vs long-term memory (LTM))[34], it is an ideal model to study memory mechanisms. In this study we first investigated the relationship of the NMDARs and LTCCs in generating somatic calcium transients in aPC pyramidal neurons, and we studied the interaction of the NMDARs and LTCCs in odor preference learning in week-old neonatal mice

Methods

Results

Conclusion