We previously reported, using fiber photometry, that operant responding reinforced by access to a peer (social self-administration) is associated with phasic dopamine increases in nucleus accumbens (NAc) core following lever insertion (reward-availability cue) and gradual increases preceding lever-pressing. Here, we sought to replicate these findings and determine whether dopamine signals (1) generalize to responding for high-carbohydrate palatable food, (2) show opposite patterns during negative reinforcement (shock avoidance/escape), and (3) depend on whether reinforcers are experienced alone or together. We trained male and female rats to lever-press for access to a same-sex peer (15 s/trial) and palatable food (45-mg pellet/trial), followed by shock avoidance/escape (0.18-0.28 mA). After training, we expressed the dopamine sensor GRAB-DA2m and implanted optic fibers into NAc core. We measured dopamine activity during sessions with either one- or three-reinforcers. During social self-administration, dopamine activity showed phasic increases following lever insertion and gradual increases preceding lever-pressing; responses were moderately greater during sessions with all three reinforcers. Palatable food self-administration showed a similar pattern, but responses were approximately twofold greater during single-reinforcer sessions. During shock avoidance/escape, dopamine activity showed phasic decreases at warning onset, lever insertion, and shock onset; responses were also greater during single-reinforcer sessions. Results suggest that NAc core dopamine signaling distinguishes positive from negative reinforcement and is modulated by reinforcer availability. Compared with single-reinforcer sessions, dopamine responses during food self-administration and shock avoidance/escape were reduced during sessions with all three reinforcers, whereas responses during social self-administration modestly increased. Nucleus accumbens (NAc) dopamine is critical for processing the valence of positive reinforcers, whereas its role in negative reinforcement is less well understood. Here, we extended our prior work on operant social self-administration to determine whether these findings generalize to food reinforcement, show the opposite pattern during operant negative reinforcement (shock avoidance/escape), and depend on whether reinforcers are experienced alone or together. Results suggest that NAc core dopamine activity differentiates positive and negative reinforcement and is modulated by the presence of other available reinforcers. Specifically, dopamine responses during food self-administration and shock avoidance/escape were reduced when all three reinforcers were available together compared with when each reinforcer was experienced alone, whereas responses during social self-administration showed the opposite pattern.

A central framework in basal ganglia neuroscience is that the cerebral cortex sends excitatory information to the striatum, where it is integrated with thalamic and neuromodulatory signals to shape action selection, learning, and behavioral flexibility [1-10]. In this classical view, the striatum acts as the major input structure of the basal ganglia, whereas processed output returns to the cortex indirectly through pallidal, nigral, and thalamocortical pathways [1-4, 10, 11]. However, recent evidence indicates that striatal and pallidal circuits can influence cortical processing through more direct, specialized, and neurochemically diverse routes than previously appreciated [12-16], revealing an unexpected diversity of basal ganglia return pathways. In particular, the identification of a previously uncharacterized cholinergic projection from the dorsal tail of the striatum to the auditory cortex suggests that specialized striatal circuits can directly modulate cortical sensory processing [15]. These findings provide a new entry point for reconsidering basal ganglia-cortical communication beyond the classical indirect loop model. In this review, we use this striato-cortical cholinergic pathway as a recent example, considered alongside the more established pallidocortical literature, to discuss the emerging concept of striato-pallidal-cortical return signaling. We first revisit the historical organization of corticostriatal and basal ganglia-thalamocortical loops, discuss the dorsal tail of the striatum as a sensory-associated basal ganglia node, and finally integrate recent evidence for direct and reciprocal pallidocortical pathways. Together, we propose an expanded model in which basal ganglia circuits may influence cortical gain, timing, sensory salience, and behavioral relevance through multiple return channels. Rather than replacing the classical model, this emerging view expands it: the striatum is not only a recipient of cortical input, but also a participant in return pathways that can contribute to shaping cortical computation.

Information flow in neurons proceeds by integrating inputs in dendrites, generating action potentials near the soma, and releasing neurotransmitters from nerve terminals in the axon. We found that in the striatum, acetylcholine-releasing neurons induce action potential firing in distal dopamine axons. Spontaneous activity of cholinergic neurons produced dopamine release that extended beyond acetylcholine-signaling domains, and traveling action potentials were readily recorded from dopamine axons in response to cholinergic activation. In freely moving mice, dopamine and acetylcholine covaried with movement direction. Local inhibition of nicotinic acetylcholine receptors impaired dopamine dynamics and affected movement. Our findings uncover an endogenous mechanism for action potential initiation independent of somatodendritic integration and establish that this mechanism segregates the control of dopamine signaling between axons and somata.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

This brief review summarizes the most recent progress in in vivo voltage imaging in the neurosciences, as an extension to the work presented at the voltage imaging session of the 2025 FENS regional meeting in Oslo. First, we outline the latest advances in genetically encoded voltage indicators. Next, we examine technical innovations that have reshaped imaging platforms and lay the groundwork to investigate neural activity in real time across large fields of view and in deep tissue. Finally, we highlight a selection of compelling applications that have emerged over the past 5 years, illustrating how voltage imaging evolved from a proof of concept to being deployed to answer pending neuroscientific questions.

Activity of the mesolimbic dopamine system has long been implicated in encoding primary rewards and contributing to the addictive properties of drugs of abuse. Dopamine neurons in the ventral tegmental area (VTA) of the midbrain typically show patterns of spontaneous burst activity that align with the onset of salient events or rewarding stimuli, resulting in phasic dopamine release in the nucleus accumbens (NAc). Fiber photometry is increasingly being used as an accessible technique to quantify neural activity with high temporal resolution at sensors offering signal specificity in stable recordings over extended periods of time. It has been well established by multiple techniques that opioids increase mesolimbic dopamine activity, likely through disinhibition of VTA neurons. Here we used fiber photometry to compare sub-second transient events from VTA neurons with GCaMP6f and dopamine release in the lateral shell of the NAc with dLight1.3b and GRABDA2h in response to morphine treatment. In weekly sessions, one dose of morphine was administered in escalating order (2.5, 5,7.5, and 10 mg/kg, intraperitoneal). Consistent with prior literature, both GCaMP6f in VTA neurons and dLight1.3b in NAc showed patterns of increased signal following morphine treatment. In contrast, morphine suppressed transient activity at GRABDA2h sensors. Further analyses of whole signal streams from each sensor showed a generalized increase, but reduction in variability of the GRABDA2h signal, consistent with the interpretation of sensor saturation. Such results emphasize the importance of the inclusion of appropriate controls to contextualize the interpretation of biosensor responses, particularly in response to pharmacological treatment.

To describe transient neonatal hyperthyroidism in a preterm infant born to a mother with Graves disease previously treated by total thyroidectomy, with no antenatal TRAb assessment and a postpartum maternal TRAb result documented as negative.