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From the 1770s through the 1840s, German, Austrian, and Swiss artists used the medium of printmaking to create works that synthesized poetry, literature, music, and the visual arts in new and captivating ways. Finding an eager audience in the growing number of educated middle-class collectors, printmakers experimented with modern technologies, such as lithography, and drew on the contemporary interest in regional folklore and traditional fairy tales to produce innovative compositions that both contributed to and reflected the dramatic cultural and political upheavals of the Romantic era. Featuring the work of more than 120 artists, including Casper David Friedrich, Ludwig Emil Grimm, Joseph Anton Koch, Philipp Otto Runge, and Johann Gottfried Schadow, this authoritative book contains many unique and never-before-published examples of prints from the Philadelphia Museum of Art's unrivaled collection.-- Source other than Library of Congress.

How is it that groups of neurons dispersed through the brain interact to generate complex behaviors? Three papers in this issue present brain-scale studies of neuronal activity and dynamics (see the Perspective by Huk and Hart). Allen et al. found that in thirsty mice, there is widespread neural activity related to stimuli that elicit licking and drinking. Individual neurons encoded task-specific responses, but every brain area contained neurons with different types of response. Optogenetic stimulation of thirst-sensing neurons in one area of the brain reinstated drinking and neuronal activity across the brain that previously signaled thirst. Gründemann et al. investigated the activity of mouse basal amygdala neurons in relation to behavior during different tasks. Two ensembles of neurons showed orthogonal activity during exploratory and nonexploratory behaviors, possibly reflecting different levels of anxiety experienced in these areas. Stringer et al. analyzed spontaneous neuronal firing, finding that neurons in the primary visual cortex encoded both visual information and motor activity related to facial movements. The variability of neuronal responses to visual stimuli in the primary visual area is mainly related to arousal and reflects the encoding of latent behavioral states. Science , this issue p. eaav3932 , p. eaav8736 , p. eaav7893 ; see also p. 236 Longitudinal large-scale imaging of amygdala activity reveals dynamic encoding of behavioral states by two distinct neural ensembles. Internal states, including affective or homeostatic states, are important behavioral motivators. The amygdala regulates motivated behaviors, yet how distinct states are represented in amygdala circuits is unknown. By longitudinally imaging neural calcium dynamics in freely moving mice across different environments, we identified opponent changes in activity levels of two major, nonoverlapping populations of basal amygdala principal neurons. This population signature does not report global anxiety but predicts switches between exploratory and nonexploratory, defensive states. Moreover, the amygdala separately processes external stimuli and internal states and broadcasts state information via several output pathways to larger brain networks. Our findings extend the concept of thalamocortical “brain-state” coding to include affective and exploratory states and provide an entry point into the state dependency of brain function and behavior in defined circuits.

A key driver of mammalian intelligence is the ability to represent incoming sensory information across multiple abstraction levels. For example, in the visual ventral stream, incoming signals are first represented as low-level edge filters and then transformed into high-level object representations. Similar hierarchical structures routinely emerge in artificial neural networks (ANNs) trained for object recognition tasks, suggesting that similar structures may underlie biological neural networks. However, the classical ANN training algorithm, backpropagation, is considered biologically implausible, and thus alternative biologically plausible training methods have been developed such as Equilibrium Propagation, Deep Feedback Control, Supervised Predictive Coding, and Dendritic Error Backpropagation. Several of those models propose that local errors are calculated for each neuron by comparing apical and somatic activities. Notwithstanding, from a neuroscience perspective, it is not clear how a neuron could compare compartmental signals. Here, we propose a solution to this problem in that we let the apical feedback signal change the postsynaptic firing rate and combine this with a differential Hebbian update, a rate-based version of classical spiking time-dependent plasticity (STDP). We prove that weight updates of this form minimize two alternative loss functions that we prove to be equivalent to the error-based losses used in machine learning: the inference latency and the amount of top-down feedback necessary. Moreover, we show that the use of differential Hebbian updates works similarly well in other feedback-based deep learning frameworks such as Predictive Coding or Equilibrium Propagation. Finally, our work removes a key requirement of biologically plausible models for deep learning and proposes a learning mechanism that would explain how temporal Hebbian learning rules can implement supervised hierarchical learning.

Pain is an unpleasant experience. How the brain’s affective neural circuits attribute this aversive quality to nociceptive information remains unknown. By means of time-lapse in vivo calcium imaging and neural activity manipulation in freely behaving mice encountering noxious stimuli, we identified a distinct neural ensemble in the basolateral amygdala that encodes the negative affective valence of pain. Silencing this nociceptive ensemble alleviated pain affective-motivational behaviors without altering the detection of noxious stimuli, withdrawal reflexes, anxiety, or reward. Following peripheral nerve injury, innocuous stimuli activated this nociceptive ensemble to drive dysfunctional perceptual changes associated with neuropathic pain, including pain aversion to light touch (allodynia). These results identify the amygdalar representations of noxious stimuli that are functionally required for the negative affective qualities of acute and chronic pain perception.

Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Previous GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores through resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than previous GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy.

Interactions with male and female intruders activated overlapping neuronal populations in the ventromedial hypothalamus of inexperienced adult male mice, and these ensembles gradually separated as the mice acquired social and sexual experience with conspecifics. Social behaviour shapes sex circuitry In the laboratory, most experimentally learned animal behaviours require training to achieve high performance, with neural circuits and ensembles changing as animals master a task. However, it is not clear whether experience can influence circuits for instinctive behaviours, which can be performed without training. Here, David Anderson and colleagues report that modifications to the neural ensembles in the hypothalamus that represent sex occur with increasing social experience. They find that inexperienced animals exhibit overlapping neural representations for male or female members of the same species introduced as intruders to their cage, but sex-specific ensembles emerged over time as mice increased their social and sexual experience. The authors conclude that innate behaviours may not always function as a 'hard-wired' system. All animals possess a repertoire of innate (or instinctive 1 , 2 ) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown 3 , 4 , 5 . Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1 + ) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents 6 , 7 , 8 . We used microendoscopy 9 to image Esr1 + neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson’s disease with the dopamine precursor l -DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during l -DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, l -DOPA or agonism of the D 2 dopamine receptor reversed these abnormalities more effectively than agonism of the D 1 dopamine receptor. The opposite pathophysiology arose in l -DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity. In mouse models of Parkinson’s disease and dyskinesia, striatal spiny projection neurons of the direct and indirect pathways have abnormal, imbalanced levels of spontaneous and locomotor-related activity, with the two different disease states characterized by opposite abnormalities.

The ability to sequentially learn multiple tasks without forgetting is a key skill of biological brains, whereas it represents a major challenge to the field of deep learning. To avoid catastrophic forgetting, various continual learning (CL) approaches have been devised. However, these usually require discrete task boundaries. This requirement seems biologically implausible and often limits the application of CL methods in the real world where tasks are not always well defined. Here, we take inspiration from neuroscience, where sparse, non-overlapping neuronal representations have been suggested to prevent catastrophic forgetting. As in the brain, we argue that these sparse representations should be chosen on the basis of feed forward (stimulus-specific) as well as top-down (context-specific) information. To implement such selective sparsity, we use a bio-plausible form of hierarchical credit assignment known as Deep Feedback Control (DFC) and combine it with a winner-take-all sparsity mechanism. In addition to sparsity, we introduce lateral recurrent connections within each layer to further protect previously learned representations. We evaluate the new sparse-recurrent version of DFC on the split-MNIST computer vision benchmark and show that only the combination of sparsity and intra-layer recurrent connections improves CL performance with respect to standard backpropagation. Our method achieves similar performance to well-known CL methods, such as Elastic Weight Consolidation and Synaptic Intelligence, without requiring information about task boundaries. Overall, we showcase the idea of adopting computational principles from the brain to derive new, task-free learning algorithms for CL.

The brain’s ability to associate different stimuli is vital for long-term memory, but how neural ensembles encode associative memories is unknown. Here we studied how cell ensembles in the basal and lateral amygdala encode associations between conditioned and unconditioned stimuli (CS and US, respectively). Using a miniature fluorescence microscope, we tracked the Ca 2+ dynamics of ensembles of amygdalar neurons during fear learning and extinction over 6 days in behaving mice. Fear conditioning induced both up- and down-regulation of individual cells’ CS-evoked responses. This bi-directional plasticity mainly occurred after conditioning, and reshaped the neural ensemble representation of the CS to become more similar to the US representation. During extinction training with repetitive CS presentations, the CS representation became more distinctive without reverting to its original form. Throughout the experiments, the strength of the ensemble-encoded CS–US association predicted the level of behavioural conditioning in each mouse. These findings support a supervised learning model in which activation of the US representation guides the transformation of the CS representation. Use of a head-mounted miniature microscope in awake, behaving mice reveals that neural ensembles in the basal and lateral amygdala encode associations between conditioned and unconditioned stimuli in a way that matches models of supervised learning. Of mice and memory decoding Most of the work exploring the substrates underlying associative memory formation has involved molecular and cellular aspects, but less is known about how neural ensembles encode these associations between stimuli. Here, Mark Schnitzer and colleagues utilize chronic microendoscopy imaging in behaving mice to observe cell ensembles within the amygdala that represent conditioned and unconditioned stimuli. As associations are formed and strengthened, the representation of the conditioned stimulus increasingly matches that of the unconditioned stimulus, with the opposite occurring during extinction of the association. These findings support a supervised learning model that could be tested in neural areas beyond the amygdala.

New three-photon miniature microscopes open the study of neuronal networks to those deep in the brains of behaving animals.