Short-term Hebbian learning can implement transformer-like attention.

Transformers have revolutionized machine learning models of language and vision, but their connection with neuroscience remains tenuous. Built from attention layers, they require a mass comparison of queries and keys that is difficult to perform using traditional neural circuits. Here, we show that neurons can implement attention-like computations using short-term, Hebbian synaptic potentiation. We call our mechanism the match-and-control principle and it proposes that when activity in an axon is synchronous, or matched, with the somatic activity of a neuron that it synapses onto, the synapse can be briefly strongly potentiated, allowing the axon to take over, or control, the activity of the downstream neuron for a short time. In our scheme, the keys and queries are represented as spike trains and comparisons between the two are performed in individual spines allowing for hundreds of key comparisons per query and roughly as many keys and queries as there are neurons in the network.

VIP Interneurons Contribute to Avoidance Behavior by Regulating Information Flow across Hippocampal-Prefrontal Networks.

Inhibitory interneurons expressing vasoactive intestinal polypeptide (VIP) are known to disinhibit cortical neurons. However, it is unclear how disinhibition, occurring at the single-cell level, interacts with network-level patterns of activity to shape complex behaviors. To address this, we examined the role of prefrontal VIP interneurons in a widely studied mouse behavior: deciding whether to explore or avoid the open arms of an elevated plus maze. VIP interneuron activity increases in the open arms and disinhibits prefrontal responses to hippocampal inputs, which are known to transmit signals related to open arm avoidance. Indeed, inhibiting VIP interneurons disrupts network-level representations of the open arms and decreases open arm avoidance specifically when hippocampal-prefrontal theta synchrony is strong. Thus, VIP interneurons effectively gate the ability of hippocampal input to generate prefrontal representations, which drive avoidance behavior. This shows how VIP interneurons enable cortical circuits to integrate specific inputs into network-level representations that guide complex behaviors. VIDEO ABSTRACT.

Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies.

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA-PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA-PFC projections elicited place preference. Furthermore, substituting phasic VTA-PFC stimulation for food rewards was not sufficient to reinforce new cue-reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue-reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue-reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA-PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA-PFC activity can control whether mice maintain or deviate from previously learned cue-reward associations.SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca2+ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA-PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue-reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects.