Asymmetrical choice-related ensemble activity in direct and indirect-pathway striatal neurons drives perceptual decisions

Action selection during decision-making depends on the basal ganglia circuits that comprise the direct and indirect pathways known to oppositely control movement. However, the mechanism for coordinating these opponent pathways during decision-making remains unclear. We address this by employing deep-brain two-photon imaging and optogenetic manipulations of the direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) in the posterior striatum during an auditory decision-making behavior. We show that while dSPNs and iSPNs play opposite causal roles during decision-making, each subtype contains divergent ensembles preferring different choices. The ensembles in dSPNs show stronger contralateral dominance than those in iSPNs manifested by higher-level activation and synchronization. Consistent with this asymmetrical contralateral dominance, optogenetic disinhibition of both pathways promoted contralateral choices. A computational model incorporating the striatal ensemble asymmetry recapitulated the causal behavioral effects. Our results uncover the asymmetry between opponent SPN ensembles as a circuit mechanism for action selection during decision-making.

Lateralization of CA1 assemblies in the absence of CA3 input

In the hippocampal circuit CA3 input plays a critical role in the organization of CA1 population activity, both during learning and sleep. While integrated spatial representations have been observed across the two hemispheres of CA1, these regions lack direct connectivity and thus the circuitry responsible remains largely unexplored. Here we investigate the role of CA3 in organizing bilateral CA1 activity by blocking synaptic transmission at CA3 terminals through the inducible transgenic expression of tetanus toxin. Although the properties of single place cells in CA1 were comparable bilaterally, we find a decrease of ripple synchronization between left and right CA1 after silencing CA3. Further, during both exploration and rest, CA1 neuronal ensemble activity is less coordinated across hemispheres. This included degradation of the replay of previously explored spatial paths in CA1 during rest, consistent with the idea that CA3 bilateral projections integrate activity between left and right hemispheres and orchestrate bilateral hippocampal coding.

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Scalable and accurate method for neuronal ensemble detection in spiking neural networks

We propose a novel, scalable, and accurate method for detecting neuronal ensembles from a population of spiking neurons. Our approach offers a simple yet powerful tool to study ensemble activity. It relies on clustering synchronous population activity (population vectors), allows the participation of neurons in different ensembles, has few parameters to tune and is computationally efficient. To validate the performance and generality of our method, we generated synthetic data, where we found that our method accurately detects neuronal ensembles for a wide range of simulation parameters. We found that our method outperforms current alternative methodologies. We used spike trains of retinal ganglion cells obtained from multi-electrode array recordings under a simple ON-OFF light stimulus to test our method. We found a consistent stimuli-evoked ensemble activity intermingled with spontaneously active ensembles and irregular activity. Our results suggest that the early visual system activity could be organized in distinguishable functional ensembles. We provide a Graphic User Interface, which facilitates the use of our method by the scientific community.

A neuronal code for space in hippocampal coactivity dynamics independent of place fields

Hippocampus CA1 place cells express a spatial neural code by discharging action potentials in cell-specific locations (′place fields′), but their discharge timing is also coordinated by multiple mechanisms, suggesting an alternative ′ensemble cofiring′ neural code, potentially distinct from place fields. We compare the importance of these distinct information representation schemes for encoding environments. Using miniature microscopes, we recorded the ensemble activity of mouse CA1 principal neurons expressing GCaMP6f across a multi-week experience of two distinct environments. We find that both place fields and ensemble coactivity relationships are similarly reliable within environments and distinctive between environments. Decoding the environment from cell-pair coactivity relationships is effective and improves after removing cell-specific place tuning. Ensemble decoding relies most crucially on anti-coactive cell pairs distributed across CA1 and is independent of place cell firing fields. We conclude that ensemble cofiring relationships constitute an advantageous neural code for environmental space, independent of place fields.

Loss of Stk11 in basolateral amygdalar projection neurons impairs CTA learning by altering the temporal pattern of taste response plasticity in GC

Gustatory cortex (GC) responds to tastes on the tongue with dynamic ensemble activity that represents first the presence, then the identity, and finally the hedonic value (palatability) of tastes. This final state of the taste response is uniquely altered by conditioned taste aversion (CTA) -- a powerful one-trial learning paradigm in which a taste becomes aversive after association with gastric malaise -- a process requiring coordination between GC and basolateral amygdala (BLA). One key requirement for learning in this circuit is expression of the serine/threonine kinase 11 (Stk11) gene (a tumor suppression gene which has only recently been associated with learning). When Stk11 is knocked out in BLA projection neurons (BLApn), CTA learning fails to occur. Here we have examined how learning-related response plasticity in GC taste responses is impacted by the knockout of Stk11 in BLApn. Contrary to the commonly held assumption that a lack of learning means a lack of such plasticity, but consistent with the fact that Stk11KO has been shown to increase the excitability of BLApn, our data reveal that the knockout of Stk11 in BLApn does not eliminate plasticity; rather, it shifts the impact of CTA training on GC taste responses to an earlier, learning-inappropriate epoch. Even naïve taste representations are altered -- specifically, the pattern of similarities and differences among the different taste responses are rendered abnormal by Stk11 KO, and these relationships fail to change with training. Finally, the latency of behavior-related dynamic ensemble features of the GC taste response, which is also abnormal in naïve KO mice, is rendered disorganized by CTA. Together, these results suggest that Stk11 plays a role in governing the coordination of GC activity by BLA, and demonstrate that alterations in the function of BLApn caused by Stk11KO inhibit learning not by inhibiting plasticity but by changing its temporal properties.

Video gaming as craft consumption

This article repurposes Campbell’s (2005) concept of ‘the craft consumer’ to generate a new theory of video game consumption, which proposes that we identify the material practices typically associated with craft labour within acts of digital play. We draw on case studies from popular and community-driven video game titles including Dark Souls and Super Mario Maker to make our argument, suggesting that a grasp of the controls initiates material practices, like repetition, which provide the groundwork for craft skill. It is from this position that we argue that consumers initiate a craft-like ‘dialogue’ (Sennett R (2008) The Craftsman. London: Yale University Press.) with the game’s design that reveals the experimental and creative nature of video game consumption. Importantly, these case studies provide evidence to meet with Campbell’s definition of ‘craft consumption’ as an (1) ‘ensemble activity’ and (2) as a ‘collection’ of handmade things. The result is a better understanding of the consumer as someone who initiates experiences of skilled labour and creative self-expression through the craft of playing a video game. This article presents a new understanding of the (gaming) consumer whilst also challenging the idea that the experience of ‘craft consumption’ is typically reserved for the middle or professional classes, as Campbell maintains.

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Lastly, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd as a central node of the escape network.