Area X is a songbird basal ganglia nucleus that is required for vocal learning. Both Area X and its immediate surround, the medial striatum (MSt), contain cells displaying either striatal or pallidal characteristics. We used pathway-tracing techniques to compare directly the targets of Area X and MSt with those of the lateral striatum (LSt) and globus pallidus (GP). We found that the zebra finch LSt projects to the GP, substantia nigra pars reticulata (SNr) and pars compacta (SNc), but not the thalamus. The GP is reciprocally connected with the subthalamic nucleus (STN) and projects to the SNr and motor thalamus analog, the ventral intermediate area (VIA). In contrast to the LSt, Area X and surrounding MSt project to the ventral pallidum (VP) and dorsal thalamus via pallidal-like neurons. A dorsal strip of the MSt contains spiny neurons that project to the VP. The MSt, but not Area X, projects to the ventral tegmental area (VTA) and SNc, but neither MSt nor Area X projects to the SNr. Largely distinct populations of SNc and VTA dopaminergic neurons innervate Area X and surrounding the MSt. Finally, we provide evidence consistent with an indirect pathway from the cerebellum to the basal ganglia, including Area X. Area X projections thus differ from those of the GP and LSt, but are similar to those of the MSt. These data clarify the relationships among different portions of the oscine basal ganglia as well as among the basal ganglia of birds and mammals.

The endoplasmic reticulum (ER) has a complex morphology comprised of stacked sheets, tubules, and three-way junctions, which together function as a platform for protein synthesis of membrane and secretory proteins. Specific ER subdomains are thought to be spatially organized to enable protein synthesis activity, but precisely where these domains are localized is unclear, especially relative to the plethora of organelle interactions taking place on the ER. Here, we use single-molecule tracking of ribosomes and mRNA in combination with simultaneous imaging of ER to assess the sites of membrane protein synthesis on the ER. We found that ribosomes were widely distributed throughout different ER morphologies, but the synthesis of membrane proteins (including Type I, II, and multi-spanning) and an ER luminal protein (Calreticulin) occurred primarily at three-way junctions. Lunapark played a key role in stabilizing transmembrane protein mRNA at three-way junctions. We additionally found that translating mRNAs coding for transmembrane proteins are in the vicinity of lysosomes and translate through a cap-independent but eIF2-dependent mechanism. These results support the idea that discrete ER subdomains co-exist with lysosomes to support specific types of protein synthesis activities, with ER-lysosome interactions playing an important role in the translation of secretome mRNAs.

Our ability to remember the past is essential for guiding our future behavior. Psychological and neurobiological features of declarative memories are known to transform over time in a process known as systems consolidation. While many theories have sought to explain the time-varying role of hippocampal and neocortical brain areas, the computational principles that govern these transformations remain unclear. Here we propose a theory of systems consolidation in which hippocampal-cortical interactions serve to optimize generalizations that guide future adaptive behavior. We use mathematical analysis of neural network models to characterize fundamental performance tradeoffs in systems consolidation, revealing that memory components should be organized according to their predictability. The theory shows that multiple interacting memory systems can outperform just one, normatively unifying diverse experimental observations and making novel experimental predictions. Our results suggest that the psychological taxonomy and neurobiological organization of declarative memories reflect a system optimized for behaving well in an uncertain future.

In the visual cortex of many mammals, orientation preference changes smoothly along the cortical surface, with the exception of singularities such as pinwheels and fractures. The reason for the existence of these singularities has remained elusive, suggesting that they are developmental artifacts. We show that singularities reduce the length of intracortical neuronal connections for some connection rules. Therefore, pinwheels and fractures could be evolutionary adaptations keeping cortical volume to a minimum. Wire length minimization approach suggests that interspecies differences in orientation preference maps reflect differences in intracortical neuronal circuits, thus leading to experimentally testable predictions. We discuss application of our model to direction preference maps.

How does wiring specificity of neural maps emerge during development? Formation of the adult olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.

Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present the engineering of a set of spectrally orthogonal fluorogen-activating tags based on the fluorescence-activating and absorption shifting tag (FAST) that are compatible with two-color, live-cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. This pair of orthogonal tags allowed the creation of a two-color cell cycle sensor capable of detecting very short, early cell cycles in zebrafish development and the development of split complementation systems capable of detecting multiple protein–protein interactions by live-cell fluorescence microscopy. The fluorescent chemogenetic reporters greenFAST and redFAST were engineered by protein engineering. They display orthogonal fluorogen recognition and spectral properties allowing efficient multicolor imaging of proteins in live cells and organisms.

In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactory afferent signals and generates oscillatory output. The mushroom body is responsible for formation and retrieval of olfactory and other memories. The format of odor representations differs significantly across these structures. Whereas representations are dense, dynamic, and seemingly redundant in the antennal lobe, they are sparse and carried by more selective neurons in the mushroom body. This transformation relies on a combination of oscillatory dynamics and intrinsic and circuit properties that act together to selectively filter and synthesize the output from the antennal lobe. These results provide direct support for the functional relevance of correlation codes and shed some light on the role of oscillatory synchronization in sensory networks.

Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50-60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7-9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.

The hippocampus exhibits a variety of distinct states of activity under different conditions. For instance the rhythmic patterns of activity orchestrated by the theta oscillation during running and REM sleep are markedly different from the large irregular activity (LIA) observed during awake resting and slow wave sleep. We found that under different levels of isoflurane anesthesia activity in the hippocampus of rats displays two distinct states which have several qualities that mirror the theta and LIA states. These data provide further evidence that the two states are intrinsic modes of the hippocampus; while also characterizing a preparation that could be useful for studying the natural activity states in hippocampus. This article is protected by copyright. All rights reserved.