Visualizing the Engram: Learning Stabilizes Odor Representations in the Olfactory Network

Abstract

The nature of memory is a central issue in neuroscience. How does our representation of the world change with learning and experience? Here we use the transcription of Arc mRNA, which permits probing the neural representations of temporally separated events, to address this in a well characterized odor learning model. Rat pups readily associate odor with maternal care. In pups, the lateralized olfactory networks are independent, permitting separate training and within-subject control. We use multiday training to create an enduring memory of peppermint odor. Training stabilized rewarded, but not nonrewarded, odor representations in both mitral cells and associated granule cells of the olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An enlarged core of stable, likely highly active neurons represent rewarded odor at both stages of the olfactory network.Odor representations in anterior piriform cortex were sparser than typical in adult rat and did not enlarge with learning. This sparser representation of odor is congruent with the maturation of lateral olfactory tract input in rat pups. Cortical representations elsewhere have been shown to be highly variable in electrophysiological experiments, suggesting brains operate normally using dynamic and network-modulated representations. The olfactory cortical representations here are consistent with the generalized associative model of sparse variable cortical representation, as normal responses to repeated odors were highly variable (ϳ70% of the cells change as indexed by Arc). Learning and memory modified rewarded odor ensembles to increase stability in a core representational component.

Arc-Expressing Neuronal Ensembles Supporting Pattern Separation Require Adrenergic Activity in Anterior Piriform Cortex: An Exploration of Neural Constraints on Learning

“…When the drug group reached criterion, there was no longer a difference in OLR from the saline group; both showed increased stability. Increased stability of cortical motor (Peters et al, 2014;Cao et al, 2015) and sensory (Shakhawat et al, 2014a;Shakhawat et al, 2014b;Poort et al, 2015) representations with learning appears to be a general feature of learning-induced network change. Ensemble sizes were similar to previous reports for aPC (ϳ4 -5%;Shakhawat et al, 2014a).…”

“…Norepinephrine (NE) release in the OB is critical for associative learning in rat pups (Wilson and Sullivan, 1994;Yuan et al, 2014). In adult rats, increases in OB NE are associated with improved signal-to-noise ratios (de Almeida et al, 2015) and lower thresholds for odor discriminations (Escanilla et al, 2010) and appear to be necessary for learning similar odor discriminations (Doucette et al, 2007;Mandairon et al, 2008).…”

“…PC pyramidal cells exhibit sparse and diffuse coding to odor input (Stettler and Axel, 2009;Poo and Isaacson, 2011;Shakhawat et al, 2014a). In addition, PC pyramidal cells project back to OB and shape mitral cell responses to odors (Boyd et al, 2015;Otazu et al, 2015).…”

Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

“…In addition, cortical engrams such as those in the retrosplenial and prefrontal cortices may support spatial navigation (Vann et al, 2009) and top-down control of memory retrieval (Tomita et al, 1999), respectively. Further, engrams in auditory (Fritz et al, 2005) and olfactory cortices Page 22 of 40 (Shakhawat et al, 2014) may support auditory recognition memory and odor-induced learned behaviors, respectively.…”

Experience-dependent plasticity in accessory olfactory bulb interneurons following male-male social interaction

“…Studies of Arc expression in the AOB show that it is selectively upregulated in subsets of AOB internal granule cells (IGCs), but not MCs, in male and female rodents after mating (Matsuoka et al, 2002a;Matsuoka et al, 2003). Arc expression by interneurons has also been noted in the main olfactory bulb in several studies (Guthrie et al, 2000;Vazdarjanova et al, 2006;Shakhawat et al, 2014). The selective expression of Arc by interneurons is atypical, and studying these populations is likely to provide new insights into the role of Arc in non-principal neuronal types.…”