ABSTRACT
The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.
ABSTRACT
OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod?el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ?ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb?uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.
ABSTRACT
The frontal lobe, the most human part of the brain (Goldberg), has been intensely studied, particularly in the last decades. This region is crucial for the control of behavior, cognition, planning, and working memory. Both behavior and higher cognitive abilities depend importantly on the arousal level, and on the autonomic responses that anticipate and accompany behaviors. In this review we will discuss the role played by the medial prefrontal cortex in controlling the level of vigilance and the autonomic and endocrine responses that are crucial for normal behavior. We will also discuss how dysfunctions of the medial prefrontal cortex resulting in the loss of the cortical control over arousal (both behavioral and vegetative) can help to explain the behavioral alterations observed in patients with posttraumatic stress, schizophrenia, attentional deficit and hyperactivity disorder and antisocial and aggressive behavior. Additionally we will discuss how studies in rats may give us valuable information about of the mechanisms by which the medial prefrontal cortex is capable of controlling the arousal state, autonomic and emotional responses in humans.
El lóbulo frontal, la parte más humana del cerebro, como lo propone E. Goldberg, ha llamado intensamente la atención de los investigadores en las últimas décadas. Esta región es clave en el control de la conducta, la personalidad, la memoria de trabajo, y en funciones cognitivas superiores. Sin embargo, tanto la conducta como las habilidades cognitivas superiores dependen de manera importante del estado de alerta, y de las respuestas autonómicas y emocionales asociadas. En esta revisión discutiremos acerca del papel que la corteza prefrontal medial juega en el control del alerta, y cómo alteraciones en la actividad de la corteza prefrontal medial, al afectar dicho control cortical, pueden explicar las alteraciones conductuales observadas en pacientes con estrés postraumático, esquizofrenia, déficit atencional y conductas antisociales y agresivas. Adicionalmente discutiremos cómo los estudios en la rata pueden darnos valiosa información sobre los mecanismos por los cuales la corteza prefrontal medial es capaz de manejar el alerta, el control autonómico y el control emocional.