Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

Abstract

Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFPϩ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFPϩ neurons were more excitable than surrounding GFPϪ neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.

Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning

“…One possible scenario is that different neuronal ensembles intermingle within PLC that encode separate learned associations or memories (Warren et al, 2016). This seems likely given the diverse role of PLC in attentional allocation, contextual encoding, and rewarding and aversive learning (Watanabe, 1996;Schall et al, 2002;Fujii and Graybiel, 2003;Euston et al, 2012;Sharpe and Killcross, 2014;Pinto and Dan, 2015). In support of this idea, recently, we demonstrated a critical role of infralimbic cortex (ILC) neuronal ensembles in both operant learning and extinction of the operant response (Warren et al, 2016).…”

“…The PLC is a functionally diverse structure within the prefrontal cortex that plays a critical role in goal-directed behavior and learning (Baldwin et al, 2002;Corbit and Balleine, 2003;Fujii and Graybiel, 2003;Euston et al, 2012) and is active during the presentation of reward or reward-predictive cues (Watanabe, 1996;Matsumoto et al, 2007;Moorman and Aston-Jones, 2015;Pinto and Dan, 2015). We then used an ex vivo brain slice preparation in FosGFP-transgenic rats (Cifani et al, 2012) to identify Fos/GFP-expressing neurons that were strongly activated during operant food self-administration and assessed intrinsic excitability in FosGFP ϩ and FosGFP Ϫ neurons.…”

Long‐term plasticity of corticostriatal synapses is modulated by pathway‐specific co‐release of opioids through κ‐opioid receptors

“…Following learning in vivo , enhanced excitability distinguishes ensembles of SPNs engaged to retain recently learned associations (Ziminski et al . ), and dorsomedial SPNs show transiently enhanced intrinsic excitability proximal to new learning (Hawes et al . ).…”

Chasing the addicted engram: identifying functional alterations in Fos-expressing neuronal ensembles that mediate drug-related learned behavior

“…While it is clear that the SK channel is an important modulator of excitability and a frequent target in studies of associative learning, its role in activity-dependent ensembles and addiction is yet to be explored. Neuronal excitability increases after learning Ziminski et al 2017Ziminski et al , 2018. (Bottom) Example of synaptic changes in a Fos neuron before and shortly after drug-based learning experience.…”

“…Synaptic alterations are likely induced during subsequent training sessions so that the relevant cue-specific inputs can more reliably and efficiently activate the most strongly activated ensemble neurons Yiu et al 2014;Whitaker et al 2016). This coupled with shifts in the intrinsic membrane properties of cue-selected ensemble neurons across training may lead to the selection of particular neurons as ensemble neurons Ziminski et al 2017Ziminski et al , 2018. However, a different line of studies found that constitutive overexpression of the transcription factor CREB "before" learning or cue experience led to preferential recruitment of lateral amygdala neurons into an ensemble encoding cue-cocaine associations, or a "cocaine engram" .…”