Positioning the Brainstem Within the Neural Network of Threat Prediction

In a recent study, Strickland and McDannald dissected the role of brainstem networks in threat prediction. Using probabilistic threat discrimination in rats, the authors demonstrated that brainstem neurons estimate threat probability and generate positive aversive prediction errors after unexpected outcomes. Their findings suggest that, beyond organizing defensive behaviors, brainstem neurons are involved in threat prediction computations

Enhancing Associative Learning in Rats With a Computationally Designed Training Protocol

Background Learning requires the activation of protein kinases with distinct temporal dynamics. In Aplysia, nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown. Methods We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear extinction experiments. Immunohistochemistry was performed to evaluate pCREB (phosphorylated cAMP response element binding)\protein levels in brain regions that have been implicated in fear acquisition. Results Rats exposed to the optimal conditioning protocol with irregular ITIs exhibited impaired extinction memory acquisition within the session using a standard footshock intensity, and stronger fear memory retrieval and spontaneous recovery with a weaker footshock intensity, compared with rats that received massed or spaced conditioning protocols with fixed ITIs. Rats exposed to the optimal extinction protocol displayed improved extinction of contextual fear memory and reduced spontaneous recovery compared with rats that received standard extinction protocols. Moreover, the optimal conditioning protocol increased pCREB levels in the dentate gyrus of the dorsal hippocampus, suggesting enhanced induction of long-term potentiation. Conclusions These findings demonstrate that a computational model–driven behavioral intervention can enhance associative learning in mammals and may provide insight into strategies to improve cognition in humans

Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

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 foodseeking 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.Fil: Fernandez Leon, Jose Alberto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Texas Health Science Center at Houston; Estados UnidosFil: Engelke, Douglas S.. University of Texas Health Science Center at Houston; Estados UnidosFil: Aquino Miranda, Guillermo. University of Texas Health Science Center at Houston; Estados UnidosFil: Goodson, Alexandria. University of Texas Health Science Center at Houston; Estados Unidos. Rice University; Estados UnidosFil: Rasheed, María N.. University of Texas Health Science Center at Houston; Estados UnidosFil: Do Monte, Fabricio H.. University of Texas Health Science Center at Houston; Estados Unidos. Rice University; Estados Unido

Sensing danger through the olfactory system: The role of the hypothalamic dorsal premammillary nucleus

The dorsal premammillary nucleus (PMd) has a critical role on the expression of defensive responses to predator odor. Anatomical evidence suggests that the PMd should also modulate memory processing through a projecting branch to the anterior thalamus. By using a pharmacological blockade of the PMd with the NMDA-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5), we were able to confirm its role in the expression of unconditioned defensive responses, and further revealed that the nucleus is also involved in influencing associative mechanisms linking predatory threats to the related context. We have also tested whether olfactory fear conditioning, using coffee odor as CS, would be useful to model predator odor. Similar to cat odor, shock-paired coffee odor produced robust defensive behavior during exposure to the odor and to the associated context. Shock-paired coffee odor also up-regulated Fos expression in the PMd, and, as with cat odor, we showed that this nucleus is involved in the conditioned defensive responses to the shock-paired coffee odor and the contextual responses to the associated environment. (C) 2008 Elsevier Ltd. All rights reserved