Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice.

Basolateral amygdala (BLA) is a key hub for affect in the brain,1,2,3 and dysfunction within this area contributes to a host of psychiatric disorders.4,5 BLA is extensively and reciprocally interconnected with frontal cortex,6,7,8,9 and some aspects of its function are evolutionarily conserved across rodents, anthropoid primates, and humans.10 Neuron density in BLA is substantially lower in primates compared to murine rodents,11 and frontal cortex (FC) is dramatically expanded in primates, particularly the more anterior granular and dysgranular areas.12,13,14 Yet, how these anatomical differences influence the projection patterns of single BLA neurons to frontal cortex across rodents and primates is unknown. Using a barcoded connectomic approach, we assessed the single BLA neuron connections to frontal cortex in mice and macaques. We found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens were similarly organized in mice and macaques, BLA-FC connections differed substantially. Notably, BLA connections to subcallosal anterior cingulate cortex (scACC) in macaques were least likely to branch to other medial frontal cortex areas compared to perigenual ACC (pgACC). This pattern of connections was reversed in the mouse homologues of these areas, infralimbic and prelimbic cortex (IL and PL), mirroring functional differences between rodents and non-human primates. Taken together, these results indicate that BLA connections to FC are not linearly scaled from mice to macaques and instead the organization of single-neuron BLA connections is distinct between these species.

Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice.

The basolateral amygdala (BLA) projects to the frontal cortex (FC) in both rodents and primates, but the comparative organization of single-neuron BLA-FC projections is unknown. Using a barcoded connectomic approach, we found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens are similarly organized in mice and macaques, BLA-FC connections differ.

A limited cerebellar contribution to suprasecond timing across differing task demands.

The involvement of the cerebellum in suprasecond interval timing (i.e., timing in the seconds to minutes range) is controversial. A limited amount of evidence from humans, nonhuman primates, and rodents has shown that the lateral cerebellum, including the lateral cerebellar nucleus (LCN), may be necessary for successful suprasecond timing performance. However, many existing studies have pitfalls, such as limited timing outcome measures and confounded task demands. In addition, many existing studies relied on well-trained subjects. This approach may be a drawback, as the cerebellum is hypothesized to carry out ongoing error correction to limit timing variability. By using only experienced subjects, past timing studies may have missed a critical window of cerebellar involvement. In the experiments described here, we pharmacologically inactivated the rat LCN across three different peak interval timing tasks. We structured our tasks to address past confounds, collect timing variability measures, and characterize performance during target duration acquisition. Across these various tasks, we did not find strong support for cerebellar involvement in suprasecond interval timing. Our findings support the existing distinction of the cerebellum as a subsecond interval timing brain region. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The dorsal hippocampus' role in context-based timing in rodents.

To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations. However, these models often overlook the fact that situational factors frequently modulate temporal expectations. For example, in realistic environments, the intervals associated with different cues will often covary due to a common underlying cause. According to the 'common cause hypothesis,' observers anticipate this covariance such that, when one cue's interval changes, temporal expectations for other cues shift in the same direction. Furthermore, as conditions will often differ across environments, the same cue can mean different things in different contexts. Therefore, updates to temporal expectations should be context-specific. Behavioral work supports these predictions, yet their underlying neural mechanisms are unclear. Here, we asked whether the dorsal hippocampus mediates context-based timing, given its broad role in context-conditioning. Specifically, we trained rats with either hippocampal or sham lesions that two cues predicted reward after either a short or long duration elapsed (e.g., tone-8 s/light-16 s). Then, we moved rats to a new context and extended the long cue's interval (e.g., light-32 s). This caused rats to respond later to the short cue, despite never being trained to do so. Importantly, when returned to the initial training context, sham rats shifted back toward both cues' original intervals. In contrast, lesion rats continued to respond at the long cue's newer interval. Surprisingly, they still showed contextual modulation for the short cue, responding earlier like shams. These data suggest the hippocampus only mediates context-based timing if a cue is explicitly paired and/or rewarded across distinct contexts. Furthermore, as lesions did not impact timing measures at baseline or acquisition for the long cue's new interval, our data suggests that the hippocampus only modulates timing when context is relevant.

No preference for prosocial helping behavior in rats with concurrent social interaction opportunities.

Helping behavior tasks are proposed to assess prosocial or "empathic" behavior in rodents. This paradigm characterizes the behavior of subject animals presented with the opportunity to release a conspecific from a distressing situation. Previous studies found a preference in rats for releasing restrained or distressed conspecifics over other controls (e.g., empty restrainers or inanimate objects). An empathy account was offered to explain the observed behaviors, claiming subjects were motivated to reduce the distress of others based on a rodent homologue of empathy. An opposing account attributes all previous results to subjects seeking social contact. To dissociate these two accounts for helping behavior, we presented subject rats with three simultaneous choice alternatives: releasing a restrained conspecific, engaging a nonrestrained conspecific, or not socializing. Subjects showed an initial preference for socializing with the nonrestrained conspecific, and no preference for helping. This result contradicts the empathy account, but is consistent with the social-contact account of helping behavior.

Why do learners ignore expected feedback in making metacognitive decisions about retrieval practice?

We report two experiments investigating why learners, in making metacognitive judgments, often seem to ignore or otherwise fail to appreciate that feedback following retrieval practice provides a restudy opportunity. Learners practiced word pairs for a final cued-recall test by studying each pair initially, making a judgment of learning (JOL), and then deciding whether to practice the pair again after a short or long spacing interval, or not at all. For different groups in Experiment 1, additional practice involved restudying, retrieval practice without feedback, or retrieval practice with feedback (the full pair). We used procedures (long feedback duration and covert retrieval practice) designed to rule out the possibility that feedback is ignored because it is usually brief or because participants' choices are influenced by a desire to look good by performing well on overt practice tests. In the relearning condition, learners preferred a long spacing interval for items at all JOL levels. Despite the feedback duration and the covert retrieval practice, learners in both retrieval-practice conditions preferred a short spacing interval for hard, low-JOL items and a long spacing interval for easy, high-JOL items, even though this may not be an effective strategy when feedback is provided. In Experiment 2, instructions framed feedback either as a presentation of the correct answer or as a restudy opportunity preceded by retrieval practice. Framing feedback as a restudy opportunity markedly changed the choices learners made. Apparently, the restudy function of feedback does not occur to learners unless they are specifically alerted to it.

Specificity and flexibility of social influence on spatial choice.

Rats searched for food in a situation that allowed them to determine which locations contained food after searching a small number of them, but not which of the baited locations contained more-preferred food rather than a less-preferred food. During some experimental trials, the latter information was available from the choices of model rats making choices together with the subject rats, because some of the model rats tended to choose the locations baited with more-preferred food. On the surface, the results suggest that social influence specified the locations of more-preferred food to the subject rats. However, more detailed analysis and data from a second experiment indicate that the social influence can be explained by a general tendency to approach another rat making choices, acquired if rats are exposed to a contingency between social approach and increased foraging success.