The effects of reward devaluation on cue-evoked modulation of sucrose seeking and neuronal ensemble plasticity in nucleus accumbens

Animals must learn the relationship between food and the environmental cues that predict their availability for the successful procurement of nutrient sources. These cues can gain powerful control over food seeking, but these cue-evoked behaviours must remain flexible and updated upon changes in internal states such as the perceived desirability of food. Recalling these cue-food associations activate subsets of neurons termed ‘neuronal ensembles’ in motivationally relevant brain areas such as the striatum. However, how neuronal ensembles are recruited and physiologically modified following the update of these learned associations has not fully elucidated. To investigate this, we examined the effects of reward devaluation on ensemble plasticity at the levels of recruitment, excitability, and synaptic physiology in sucrose conditioned Fos-GFP mice that express green fluorescent protein (GFP) in recently activated neurons. Neuronal ensemble activation patterns and their physiology were examined using immunohistochemistry and ex vivo electrophysiology, respectively. First, devaluation via four days of ad libitum sucrose consumption, but not caloric satiation, attenuated the ability of the cue to evoke sucrose seeking. Thus, changes in the hedonic, incentive value of sucrose, and not caloric need drove cue-induced sucrose seeking. Also, devaluation attenuated the cue’s ability to recruit a neuronal ensemble in nucleus accumbens (NAc), but not dorsal striatum. Next, devaluation prevented the cue from recruiting a hyper-excitable, GFP+ ensemble in the NAc, but did not alter the physiology of excitatory synapses on these GFP+ neurons. Our findings provide new insights into how updates in the hedonic value of sucrose critically modulates the flexibility of sucrose seeking and recruitment of ensembles with an altered excitability phenotype in the NAc shell

A combinatory genetic strategy for targeting neurogliaform neurons in the mouse basolateral amygdala

The mouse basolateral amygdala (BLA) contains various GABAergic interneuron subpopulations, which have distinctive roles in the neuronal microcircuit controlling numerous behavioral functions. In mice, roughly 15% of the BLA GABAergic interneurons express neuropeptide Y (NPY), a reasonably characteristic marker for neurogliaform cells (NGFCs) in cortical-like brain structures. However, genetically labeled putative NPY-expressing interneurons in the BLA yield a mixture of interneuron subtypes besides NGFCs. Thus, selective molecular markers are lacking for genetically accessing NGFCs in the BLA. Here, we validated the NGFC-specific labeling with a molecular marker, neuron-derived neurotrophic factor (NDNF), in the mouse BLA, as such specificity has been demonstrated in the neocortex and hippocampus. We characterized genetically defined NDNF-expressing (NDNF+) GABAergic interneurons in the mouse BLA by combining the Ndnf-IRES2-dgCre-D transgenic mouse line with viral labeling, immunohistochemical staining, and in vitro electrophysiology. We found that BLA NDNF+ GABAergic cells mainly expressed NGFC neurochemical markers NPY and reelin (Reln) and exhibited small round soma and dense axonal arborization. Whole-cell patch clamp recordings indicated that most NDNF+ interneurons showed late spiking and moderate firing adaptation. Moreover, ∼81% of BLA NDNF+ cells generated retroaxonal action potential after current injections or optogenetic stimulations, frequently developing into persistent barrage firing. Optogenetic activation of the BLA NDNF+ cell population yielded both GABAA- and GABAB receptor-mediated currents onto BLA pyramidal neurons (PNs). We demonstrate a combinatory strategy combining the NDNF-cre mouse line with viral transfection to specifically target adult mouse BLA NGFCs and further explore their functional and behavioral roles