Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex.

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus.

Enhancing Associative Learning in Rats With a Computationally Designed Training Protocol.

Background: Learning requires the activation of protein kinases with distinct temporal dynamics. In , 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.

A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats.

Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict.

Understanding the dynamic and destiny of memories.

Memory formation enables the retention of life experiences overtime. Based on previously acquired information, organisms can anticipate future events and adjust their behaviors to maximize survival. However, in an ever-changing environment, a memory needs to be malleable to maintain its relevance.

A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion.

Adult mammalian brains have largely lost neuroregeneration capability except for a few niches. Previous studies have converted glial cells into neurons, but the total number of neurons generated is limited and the therapeutic potential is unclear. Here, we demonstrate that NeuroD1-mediated in situ astrocyte-to-neuron conversion can regenerate a large number of functional new neurons after ischemic injury.

Boosting of Thalamic D2 Dopaminergic Transmission: A Potential Strategy for Drug-Seeking Attenuation.

This commentary focuses on novel findings by Clark et al. (2017) published in , which show that dopamine D2 receptors (D2Rs) in the paraventricular nucleus of the thalamus (PVT) are involved in cocaine sensitization. We extend the discussion on how their findings contribute to our understanding of the role of the PVT in drug seeking by providing new insight on the role of the PVT in the regulation of food-seeking and fear responses.

Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission.

The paraventricular nucleus of the thalamus (PVT) is thought to regulate behavioral responses under emotionally arousing conditions. Reward-associated cues activate PVT neurons; however, the specific PVT efferents regulating reward seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT activity under two emotionally distinct conditions: (1) when reward was available during the cue as expected or (2) when reward was unexpectedly omitted during the cue.

Revisiting the role of infralimbic cortex in fear extinction with optogenetics.

Previous rodent studies have implicated the infralimbic (IL) subregion of the medial prefrontal cortex in extinction of auditory fear conditioning. However, these studies used pharmacological inactivation or electrical stimulation techniques, which lack temporal precision and neuronal specificity. Here, we used an optogenetic approach to either activate (with channelrhodopsin) or silence (with halorhodopsin) glutamatergic IL neurons during conditioned tones delivered in one of two phases: extinction training or extinction retrieval.

Enhancement of fear extinction with deep brain stimulation: evidence for medial orbitofrontal involvement.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces anxiety, fear, and compulsive symptoms in patients suffering from refractory obsessive-compulsive disorder. In a rodent model, DBS-like high-frequency stimulation of VS can either enhance or impair extinction of conditioned fear, depending on the location of electrodes within VS (dorsal vs ventral). As striatal DBS activates fibers descending from the cortex, we reasoned that the differing effects on extinction may reflect differences in cortical sources of fibers passing through dorsal-VS and ventral-VS.

A temporal shift in the circuits mediating retrieval of fear memory.

Fear memories allow animals to avoid danger, thereby increasing their chances of survival. Fear memories can be retrieved long after learning, but little is known about how retrieval circuits change with time. Here we show that the dorsal midline thalamus of rats is required for the retrieval of auditory conditioned fear at late (24 hours, 7 days, 28 days), but not early (0.

Long-range GABAergic neurons in the prefrontal cortex modulate behavior.

Cortical glutamatergic projections are extensively studied in behavioral neuroscience, whereas cortical GABAergic projections to downstream structures have been overlooked. A recent study by Lee and colleagues (Lee AT, Vogt D, Rubenstein JL, Sohal VS. J Neurosci 34: 11519-11525, 2014) used optogenetic and electrophysiological techniques to characterize a behavioral role for long-projecting GABAergic neurons in the medial prefrontal cortex.

Hippocampal--prefrontal BDNF and memory for fear extinction.

Infusing brain-derived neurotrophic factor (BDNF) into the infralimbic (IL) prefrontal cortex is capable of inducing extinction. Little is known, however, about the circuits mediating BDNF effects on extinction or the extent to which extinction requires BDNF in IL. Using local pharmacological infusion of BDNF protein, or an antibody against BDNF, we found that BDNF in the IL, but not prelimbic (PL) prefrontal cortex, is both necessary and sufficient for fear extinction.

Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD), and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al., 2012).

[Discovery and follow-up of a lead-poisoning outbreak in a shantytown of Le Port, Reunion Island].

Background: A national survey conducted in 2008-2009 by the French Institute for Public Health Surveillance for detection of lead impact in childhood identified a high blood lead level in a young boy living in the town of "Le Port", Reunion Island. Previously, cases of lead-poisoning on the island had been exceptional; only a dozen cases were reported in the 1980s in adults, related to the use of lead-containing instruments for food preparations.

Methods: The family of the index case was invited to participate in screening tests and an environmental investigation was conducted using a standardized questionnaire.

A time-dependent role of midline thalamic nuclei in the retrieval of fear memory.

Increasing evidence indicates that the medial prefrontal cortex (mPFC) and the amygdala mediate expression and extinction of conditioned fear, but few studies have examined the inputs to these structures. The dorsal part of the midline thalamus (dMT) contains structures such as the mediodorsal nucleus, paraventricular nucleus, and paratenial nucleus that project prominently to mPFC, as well as to basal (BA) and central (Ce) nuclei of the amygdala. Using temporary inactivation with GABA agonist muscimol, we found that dMT was necessary for retrieving auditory fear memory that was 24 h old, but not 2-8 h old.

Role of beta-adrenergic receptors in the ventromedial prefrontal cortex during contextual fear extinction in rats.

It has been reported that stress-related activation of the noradrenergic system strengthens the formation of aversive memories and that beta-adrenergic receptors seem to be involved in this emotional memory processing. In this study, the effects of beta-adrenergic compounds on the extinction of contextual conditioned fear responses were evaluated. Rats were trained with footshock in a conditioning box.

Impairment of contextual conditioned fear extinction after microinjection of alpha-1-adrenergic blocker prazosin into the medial prefrontal cortex.

Long-lasting memories of aversive or stressful events have been associated with the noradrenergic system activation. Alpha-1-adrenergic antagonist prazosin has successfully been used in the last years to treat anxiety disorders related to aversive memories recurrence in humans. Contextual conditioned fear extinction paradigm in rats has been used to better understand the mechanisms involved in the attenuation of defensive behaviour after a traumatic situation.

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.