Loss of promoter IV-driven BDNF expression impacts oscillatory activity during sleep, sensory information processing and fear regulation.

Posttraumatic stress disorder is characterized by hyperarousal, sensory processing impairments, sleep disturbances and altered fear regulation; phenotypes associated with changes in brain oscillatory activity. Molecules associated with activity-dependent plasticity, including brain-derived neurotrophic factor (BDNF), may regulate neural oscillations by controlling synaptic activity. BDNF synthesis includes production of multiple Bdnf transcripts, which contain distinct 5' noncoding exons. We assessed arousal, sensory processing, fear regulation and sleep in animals where BDNF expression from activity-dependent promoter IV is disrupted (Bdnf-e4 mice). Bdnf-e4 mice display sensory hyper-reactivity and impaired electrophysiological correlates of sensory information processing as measured by event-related potentials (ERP). Utilizing electroencephalogram, we identified a decrease in slow-wave activity during non-rapid eye movement sleep, suggesting impaired sleep homeostasis. Fear extinction is controlled by hippocampal-prefrontal cortical BDNF signaling, and neurophysiological communication patterns between the hippocampus (HPC) and medial prefrontal cortex (mPFC) correlate with behavioral performance during extinction. Impaired fear extinction in Bdnf-e4 mice is accompanied by increased HPC activation and decreased HPC-mPFC theta phase synchrony during early extinction, as well as increased mPFC activation during extinction recall. These results suggest that activity-dependent BDNF signaling is critical for regulating oscillatory activity, which may contribute to altered behavior.

Rapid antidepressant effects: moving right along.

Available treatments for depression have significant limitations, including low response rates and substantial lag times for response. Reports of rapid antidepressant effects of a number of compounds, including the glutamate N-methyl-D-aspartate receptor antagonist ketamine, have spurred renewed translational neuroscience efforts aimed at elucidating the molecular and cellular mechanisms of action that result in rapid therapeutic response. This perspective provides an overview of recent advances utilizing compounds with rapid-acting antidepressant effects, discusses potential mechanism of action and provides a framework for future research directions aimed at developing safe, efficacious antidepressants that achieve satisfactory remission not only by working rapidly but also by providing a sustained response.

The behavioral treatment of auditory hallucinatory responding of a schizophrenic patient.

This study assessed the efficacy of a behaviorally based treatment package to decrease the frequency of verbal responding to auditory hallucinations and to increase attention to important external stimuli, rather than to the hallucinations. The subject, a 49-year-old male, with a 20-year history of auditory hallucinatory responding (AHR), laughing and talking to himself, was seen in an outpatient clinic. Observations were made during management skill training, given usually twice a week. Observation sessions were divided into 15-minute intervals. The intervention package included reinforcement in the form of praise, pats on the back, and token reinforcement contingent on the absence of auditory hallucinations. Cancellation tests were given to measure his ability to attend to external tasks. Using an ABCAD design, it was seen that the data indicated that the intervention resulted in both a sharp decrease in auditory hallucinations and an increase in the subject's ability to attend to external tasks.

Maintained nodal-distance effects in equivalence classes.

Twelve subjects were trained to select one of two stimuli from a pair (the B pair) when presented with one of two stimuli from another pair (the A pair), thus establishing two AB relations, A1-B1 and A2-B2. In a similar fashion, additional stimuli were used to establish BC, CD, and DE relations. Trials used to train all relations occurred in each session. Once performances were established, probe trials were introduced that tested for the emergence of untrained relations (e.g., B1-D1 or A1-E1). These emergent relations were categorized according to nodal distance (i.e., the number of stimuli across which transitivity would have to hold in order for the relation to emerge). For example, a test for A2-C2 crosses one node (B2), whereas a test for A1-E1 crosses three nodes (B1, C1, and D1). Only 2 of the subjects formed equivalence classes. The evocation of class-appropriate responding by each emergent-relation probe was an inverse function of nodal distance for all 12 subjects. In addition, performance on the originally trained relations was disrupted by the introduction of probes. The 2 subjects who exhibited equivalence classes were then trained to make different numbers of key presses in the presence of each of the four A and E stimuli. In a response-transfer test, the B, C, and D stimuli evoked the responses trained to the A and E stimuli in the same equivalence class. Likelihood of class-appropriate responses was an inverse function of nodal distance, and this pattern persisted across testing. Reaction times in the transfer test were an inverted U-shaped function of nodal distance. Because training of the baseline relations occurred concurrently and the B, C, and D stimuli were presented an equal number of times before the transfer test, the test performances illustrate effects of nodal distance that were not confounded by order or amount of experience with the stimuli. The results imply that ordered, sequential exposure to individual stimulus relations may facilitate the development of equivalence classes and that the relatedness of stimuli within an equivalence class is a relatively permanent inverse function of nodal distance.