The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: i) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.
The dopaminergic and histaminergic systems are the first to appear during the development of the nervous system. Through the activation of H
1
receptors (H
1
Rs), histamine increases neurogenesis of the cortical deep layers, while reducing the dopaminergic phenotype (cells immunoreactive to tyrosine hydroxylase, TH
+
) in embryo ventral mesencephalon. Although the function of histamine in neuronal differentiation has been studied, the role of H
1
Rs in neurogenesis has not been addressed. For this purpose, the H
1
R antagonist/inverse agonist chlorpheniramine was systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats (gestational days 12–14, E12–14), and control and experimental embryos (E14 and E16) and pups (21-day-old) were evaluated for changes in nigro-striatal development. Western blot and immunohistochemistry determinations showed a significant increase in the dopaminergic markers’ TH and PITX3 in embryos from chlorpheniramine-treated rats at E16. Unexpectedly, 21-day-old pups from the chlorpheniramine-treated group, showed a significant reduction in TH immunoreactivity in the substantia nigra
pars compacta
and dorsal striatum. Furthermore, striatal dopamine content, evoked [
3
H]-dopamine release and methamphetamine-stimulated motor activity were significantly lower compared to the control group. These results indicate that H
1
R blockade at E14–E16 favors the differentiation of dopaminergic neurons, but hampers their migration, leading to a decrease in dopaminergic innervation of the striatum in post-natal life.
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