Single Unit publications

Subcortical structures like the locus coeruleus (LC) are well known to regulate pupil-linked autonomic arousal, while the role of cortical circuits in this process remains largely unclear. We designed a closed-loop optogenetic system to inactivate the anterior cingulate cortex (ACC) in real time during pupil dilations. ACC inactivation decreased the magnitude of spontaneous pupil events. In parallel, ACC population activity scaled with the magnitude of spontaneously occurring pupil dilations. In addition to modulating spontaneous arousal, ACC responses to salient sensory stimuli scaled with the size of evoked pupil dilations and ACC inactivation suppressed saliency-linked pupil events. Last, we show that LC norepinephrine neurons signal arousal faster than the ACC. However, unlike the ACC, LC responses did not scale with the magnitude of pupil dilations. Collectively, our experiments identify the ACC as a key cortical site for sustaining momentary increases in pupil-linked arousal.

The ability to associate environmental stimuli with positive outcomes is a fundamental form of learning. While extensive research has focused on midbrain dopamine neurons during associative learning, less is known about learning-mediated changes in the afferents that shape dopamine neuron responses. We demonstrate in rats that during critical phases of learning, anion homeostasis in midbrain inhibitory GABA neurons - a primary source of input to dopamine neurons - is disrupted due to downregulation of the potassium chloride cotransporter KCC2. This alteration in GABA neurons preferentially impacted lateral mesoaccumbal dopamine pathways and was not observed after learning was established. At the network level, learning-mediated KCC2 downregulation was associated with enhanced synchronization between individual GABA neurons and increased dopamine responses to rewards and reward-related stimuli. Conversely, enhancing KCC2 function during learning reduced GABA synchronization, diminished relevant dopamine signaling, and prevented cue-reward associations. Thus, circuit-specific adaptations in midbrain GABA neurons are crucial for forming new reward-related behaviors.

Sniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The systems which influence the display of sniffing are unclear. Here, we report that dopamine release into the ventral striatum in mice is coupled with bouts of sniffing and that stimulation of dopaminergic terminals in these regions drives increases in respiratory rate to initiate sniffing whereas inhibition of these terminals reduces respiratory rate. Both the firing of individual neurons and the activity of post-synaptic D1 and D2 dopamine receptor-expressing neurons are coupled with sniffing and local antagonism of D1 and D2 receptors squelches sniffing. Together, these results support a model whereby sniffing can be initiated by dopamine's actions upon ventral striatum neurons. The nature of sniffing being integral to both olfaction and motivated behaviors implicates this circuit in a wide array of functions.

The increasing prevalence of cannabis use during pregnancy has raised medical concerns, primarily related to Δ9-tetrahydrocannabinol (THC), which readily crosses the placenta and affects fetal brain development. Previous research has identified dopaminergic alterations related to maternal THC consumption. However, the consequences that prenatal cannabis exposure (PCE) has on striatum-based processing during reward pursuit have not been determined. Here, we characterize PCE rats during food or opioid-maintained reward seeking. We find that the supramotivational phenotype of PCE rats is independent of value-based processing and is instead related to augmented reinforcing efficiency of opioid rewards. Our findings reveal that prenatal THC exposure leads to increased cue-evoked dopamine responses and an overrepresentation of effort-driven striatal encoding patterns. Recapitulating clinical findings, drug-related PCE adaptations were more pronounced in males, who showed increased vulnerability for relapse. Collectively, these findings indicate that prenatal THC exposure in male rats engenders a pronounced neurodevelopmental susceptibility to addiction-like disorders.

Local field potential (LFP) recording is a valuable method for assessing brain systems communication. Multiple methods have been developed to collect LFP data to study the rhythmic activity of the brain. These methods range from the use of single or bundled metal electrodes to electrode arrays that can target multiple brain regions. Although these electrodes are efficient in collecting LFP activity, they can be expensive, difficult to build, and less adaptable to different applications, which may include targeting multiple brain regions simultaneously. Here, the building process for a 16-channel customizable multielectrode array (CMEA) that can be used to collect LFP data from different brain regions simultaneously in rats is described. These CMEA electrode arrays are lightweight (<1 g), take little time to build (<1 h), and are affordable ($15 Canadian). The CMEA can also be modified to record single-unit and multiunit activity in addition to LFP activity using both wired and wireless neural data acquisition systems. Moreover, these CMEAs can be used to explore neural activity (LFP and single-unit/multiunit activity) in preliminary studies, before purchasing more expensive electrodes for targeted studies. Together, these characteristics make the described CMEA a competitive alternative to the commercially available multielectrode arrays for its simplicity, low cost, and efficiency in collecting LFP data in freely behaving animals.

The question of how the brain links behavioral and biological features of defensive responses has remained elusive. The importance of this problem is underscored by the observation that behavioral passivity in stress coping is associated with elevations in glucocorticoid hormones, and each may carry risks for susceptibility to a host of stress-related diseases. Past work implicates the medial prefrontal cortex (mPFC) in the top-down regulation of stress-related behaviors; however, it is unknown whether such changes have the capacity to buffer against the longer-lasting biological consequences associated with aversive experiences. Using the shock probe defensive burying test in rats to naturalistically measure behavioral and endocrine features of coping, we observed that the active behavioral component of stress coping is associated with increases in activity along a circuit involving the caudal mPFC and midbrain dorsolateral periaqueductal gray (PAG). Optogenetic manipulations of the caudal mPFC-to-dorsolateral PAG pathway bidirectionally modulated active (escape and defensive burying) behaviors, distinct from a rostral mPFC–ventrolateral PAG circuit that instead limited passive (immobility) behavior. Strikingly, under conditions that biased rats toward a passive coping response set, including exaggerated stress hormonal output and increased immobility, excitation of the caudal mPFC–dorsolateral PAG projection significantly attenuated each of these features. These results lend insight into how the brain coordinates response features to overcome passive coping and may be of importance for understanding how activated neural systems promote stress resilience.