Inhibition of norepinephrine signaling during a sensitive period disrupts locus coeruleus circuitry and emotional behaviors in adulthood.

Deficits in arousal and stress responsiveness are a feature of numerous psychiatric disorders including depression and anxiety. Arousal is supported by norepinephrine (NE) released from specialized brainstem nuclei, including the locus coeruleus (LC) neurons into cortical and limbic areas. During development, the NE system matures in concert with increased exploration of the animal's environment.

Photoactivatable Cre recombinase 3.0 for in vivo mouse applications.

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0.

Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior.

Long-range synchronization of neural oscillations correlates with distinct behaviors, yet its causal role remains unproven. In mice, tests of avoidance behavior evoke increases in theta-frequency (∼8 Hz) oscillatory synchrony between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). To test the causal role of this synchrony, we dynamically modulated vHPC-mPFC terminal activity using optogenetic stimulation.

Serotonin Subsystems Modulate Diverse and Opposite Behavioral Functions.

Pioneering work showed that serotonin (5-HT) neurons have the unique capacity to engage in different and opposed aspects of motivated behaviors such as reward and punishment responses. These findings provided strong evidence about the functional heterogeneity of 5-HT neurons, and their possible engagement in multiple and behaviorally distinct neural subsystems. A recent study provides further compelling evidence supporting this notion, in which two ascending 5-HT circuits modulate opposed aspects of motivated behaviors.

Serotonin Signaling through Prefrontal Cortex 5-HT Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors.

Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT) plays an important role in refining the formation of brain circuits during sensitive developmental periods. In rodents, the role of 5-HT receptors in general and autoreceptors in particular has been characterized in anxiety.

5-HT 1A Agonist Properties Contribute to a Robust Response to Vilazodone in the Novelty Suppressed Feeding Paradigm.

Background: Differences in 5-HT 1A receptor function have been implicated in vulnerability to depression and in response to treatment. Adding 5-HT 1A partial agonists to selective serotonin reuptake inhibitors has been touted as a strategy to increase their efficacy. Here we use the novelty suppressed feeding paradigm to compare the effects of vilazodone, a high-potency selective serotonin reuptake inhibitor, with high affinity for 5-HT 1A receptors to the reference selective serotonin reuptake inhibitor fluoxetine across several mouse strains that differ in their response to selective serotonin reuptake inhibitors.

Direct Ventral Hippocampal-Prefrontal Input Is Required for Anxiety-Related Neural Activity and Behavior.

The ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) are each required for the expression of anxiety-like behavior. Yet the role of each individual element of the circuit is unclear. The projection from the vHPC to the mPFC has been implicated in anxiety-related neural synchrony and spatial representations of aversion.

5-HT1A Autoreceptors in the Dorsal Raphe Nucleus Convey Vulnerability to Compulsive Cocaine Seeking.

Cocaine addiction and depression are comorbid disorders. Although it is well recognized that 5-hydroxytryptamine (5-HT; serotonin) plays a central role in depression, our understanding of its role in addiction is notably lacking. The 5-HT system in the brain is carefully controlled by a combined process of regulating 5-HT neuron firing through 5-HT autoreceptors, neurotransmitter release, enzymatic degradation, and reuptake by transporters.

5-HT(1A) [corrected] receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function.

Rationale: Serotonin (5-HT) neurotransmission is intimately linked to anxiety and depression and a diverse body of evidence supports the involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT(1A)) subtype, in both disorders.

Objectives: In this review, we examine the function of 5-HT(1A) receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT(1A) receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors.

Results: It is difficult to unambiguously distinguish the effects of different populations of the 5-HT(1A) receptors with traditional genetic animal models and pharmacological approaches.

Rethinking 5-HT1A receptors: emerging modes of inhibitory feedback of relevance to emotion-related behavior.

The complexities of the involvement of the serotonin transmitter system in numerous biological processes and psychiatric disorders is, to a substantial degree, attributable to the large number of serotonin receptor families and subtypes that have been identified and characterized for over four decades. Of these, the 5-HT(1A) receptor subtype, which was the first to be cloned and characterized, has received considerable attention based on its purported role in the etiology and treatment of mood and anxiety disorders. 5-HT(1A) receptors function both at presynaptic (autoreceptor) and postsynaptic (heteroreceptor) sites.

Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway.

Unraveling the mechanisms of 5-HT neuron control might provide new insights into depression pathophysiology. In addition to the inhibitory 5-HT1A autoreceptors, cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT activity in the DRN. Here we studied how decreased VGLUT1 levels in the brain stem affect glutamate regulation of 5-HT function.

Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1.

Depression has been linked to failure in synaptic plasticity originating from environmental and/or genetic risk factors. The chronic mild stress model regulates the expression of synaptic markers of neurotransmitter function and associated depressive-like behaviour. Moreover, mice heterozygous for the synaptic vesicle protein vesicular glutamate transporter 1 (VGLUT1), have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour.

Sustained stress-induced changes in mice as a model for chronic depression.

Rationale: Major depression is a chronic disabling disorder, often preceded by stress. Despite emerging clinical interest in mechanisms perpetuating episodes of depression and/or establishing increased vulnerability for relapse, little attention has been paid to address these aspects in experimental models. Here, we studied the long-term neuroadaptive effects of chronic mild stress (CMS) as well as the effectiveness of a course of an antidepressant treatment.

Increased vulnerability to depressive-like behavior of mice with decreased expression of VGLUT1.

Background: Many studies link depression to an increase in the excitatory-inhibitory ratio in the forebrain. Presynaptic alterations in a shared pathway of the glutamate/gamma-aminobutyric acid (GABA) cycle may account for this imbalance. Evidence suggests that decreased vesicular glutamate transporter 1 (VGLUT1) levels in the forebrain affect the glutamate/GABA cycle and induce helpless behavior.