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

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.

Brain activation induced by chronic psychosocial stress in mice

“…∆FOSB cell counts were acquired from 18 relevant brain regions (see Table 1 ) from 3–6 sections from each animal. The piriform cortex (Pir), an olfactory processing region 60 , was included due to its expected lack of involvement in CSDS. Exclusion criteria for single cell count data points was a deviation of ≥3 times the interquartile range below or above the median of the group.…”

β-Adrenoceptor activation enhances L-type calcium channel currents in anterior piriform cortex pyramidal cells of neonatal mice: implication for odor learning

“…In the hippocampus, LTCCs mediate protein synthesis sensitive, NMDAR-independent late phase LTP and spatial learning (Grover and Teyler 1990;Moosmang et al 2005). However, in the aPC, we have shown that LTCC activation is dependent on NMDAR activation and both channels play critical but distinct roles in the early odor preference learning (Mukherjee and Yuan 2016). Here either D-APV or nifedipine blocked isoproterenol induced learning (Fig.…”

“…1C). The larger portion of the LTCC current in P7-10 pups correlates with a highly plastic period in which LTCC-dependent early odor preference learning occurs (Jerome et al 2012;Mukherjee and Yuan, 2016). Figure 2A and B demonstrated effects of isoproterenol on the whole-cell calcium currents in the two age groups.…”

The Role of L-type Calcium Channels in Olfactory Learning and Its Modulation by Norepinephrine

“…Using calcium imaging in aPC slices, Mukherjee and Yuan ( 2016 ) demonstrated that LTCC activation is subsequent to NMDAR activation. Behaviorally, it was shown that LTCCs are required for early odor preference LTM but STM can still occur without LTCC activation.…”

“…LTM requires PKA-activated CREB signaling as it is both protein synthesis and transcription dependent (Yuan et al, 2003 ; McLean et al, 2005 ; Grimes et al, 2011 ). Owing to their location in the somatic membrane and at the base of the apical dendrite (Mukherjee and Yuan, 2016 ), LTCCs could be a fit candidate to bridge synaptic excitation and provide necessary calcium to the soma, activating kinases which subsequently phosphorylate CREB to initiate transcription in the nucleus and ultimately protein synthesis. Activation of LTCCs following NMDAR activation in the aPC is consistent with this hypothesis (see Figure 1 ).…”