Regional specialization manifests in the reliability of neural population codes.

The brain has the remarkable ability to learn and guide the performance of complex tasks. Decades of lesion studies suggest that different brain regions perform specialized functions in support of complex behaviors1-3. Yet recent large-scale studies of neural activity reveal similar patterns of activity and encoding distributed widely throughout the brain4-6. How these distributed patterns of activity and encoding are compatible with regional specialization of brain function remains unclear. Two frontal brain regions, the dorsal medial prefrontal cortex (dmPFC) and orbitofrontal cortex (OFC), are a paradigm of this conundrum. In the setting complex behaviors, the dmPFC is necessary for choosing optimal actions2,7,8, whereas the OFC is necessary for waiting for3,9 and learning from2,7,9-12 the outcomes of those actions. Yet both dmPFC and OFC encode both choice- and outcome-related quantities13-20. Here we show that while ensembles of neurons in the dmPFC and OFC of rats encode similar elements of a cognitive task with similar patterns of activity, the two regions differ in when that coding is consistent across trials ("reliable"). In line with the known critical functions of each region, dmPFC activity is more reliable when animals are making choices and less reliable preceding outcomes, whereas OFC activity shows the opposite pattern. Our findings identify the dynamic reliability of neural population codes as a mechanism whereby different brain regions may support distinct cognitive functions despite exhibiting similar patterns of activity and encoding similar quantities.

Spyglass: a framework for reproducible and shareable neuroscience research.

Scientific progress depends on reliable and reproducible results. Progress can also be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data typically involve bespoke formats and software that make replication, as well as the subsequent reuse of data, difficult if not impossible. To address these challenges, we created Spyglass, an open-source software framework that enables reproducible analyses and sharing of data and both intermediate and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for several core analyses in neuroscience, including spectral filtering, spike sorting, pose tracking, and neural decoding. It can be easily extended to apply both existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

Dual credit assignment processes underlie dopamine signals in a complex spatial environment.

Dopamine in the nucleus accumbens helps motivate behavior based on expectations of future reward ("values"). These values need to be updated by experience: after receiving reward, the choices that led to reward should be assigned greater value. There are multiple theoretical proposals for how this credit assignment could be achieved, but the specific algorithms that generate updated dopamine signals remain uncertain. We monitored accumbens dopamine as freely behaving rats foraged for rewards in a complex, changing environment. We observed brief pulses of dopamine both when rats received reward (scaling with prediction error), and when they encountered novel path opportunities. Furthermore, dopamine ramped up as rats ran towards reward ports, in proportion to the value at each location. By examining the evolution of these dopamine place-value signals, we found evidence for two distinct update processes: progressive propagation along taken paths, as in temporal-difference learning, and inference of value throughout the maze, using internal models. Our results demonstrate that within rich, naturalistic environments dopamine conveys place values that are updated via multiple, complementary learning algorithms.

Dual credit assignment processes underlie dopamine signals in a complex spatial environment.

Animals frequently make decisions based on expectations of future reward ("values"). Values are updated by ongoing experience: places and choices that result in reward are assigned greater value. Yet, the specific algorithms used by the brain for such credit assignment remain unclear. We monitored accumbens dopamine as rats foraged for rewards in a complex, changing environment. We observed brief dopamine pulses both at reward receipt (scaling with prediction error) and at novel path opportunities. Dopamine also ramped up as rats ran toward reward ports, in proportion to the value at each location. By examining the evolution of these dopamine place-value signals, we found evidence for two distinct update processes: progressive propagation of value along taken paths, as in temporal difference learning, and inference of value throughout the maze, using internal models. Our results demonstrate that within rich, naturalistic environments dopamine conveys place values that are updated via multiple, complementary learning algorithms.

Imagination as a fundamental function of the hippocampus.

Imagination is a biological function that is vital to human experience and advanced cognition. Despite this importance, it remains unknown how imagination is realized in the brain. Substantial research focusing on the hippocampus, a brain structure traditionally linked to memory, indicates that firing patterns in spatially tuned neurons can represent previous and upcoming paths in space. This work has generally been interpreted under standard views that the hippocampus implements cognitive abilities primarily related to actual experience, whether in the past (e.g. recollection, consolidation), present (e.g. spatial mapping) or future (e.g. planning). However, relatively recent findings in rodents identify robust patterns of hippocampal firing corresponding to a variety of alternatives to actual experience, in many cases without overt reference to the past, present or future. Given these findings, and others on hippocampal contributions to human imagination, we suggest that a fundamental function of the hippocampus is to generate a wealth of hypothetical experiences and thoughts. Under this view, traditional accounts of hippocampal function in episodic memory and spatial navigation can be understood as particular applications of a more general system for imagination. This view also suggests that the hippocampus contributes to a wider range of cognitive abilities than previously thought. This article is part of the theme issue 'Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny'.

Different macaque models of cognitive aging exhibit task-dependent behavioral disparities.

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques (Macaca mulatta and Macaca radiata) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan.