Predictive coding: A distinction - without a difference.

Influential models hold that neurons in the cerebral cortex signal the difference between actual and expected inputs. A new study instead finds that cortical prediction errors reflect not subtraction but rather stimulus-specific amplification of unexpected inputs.

An opponent striatal circuit for distributional reinforcement learning.

Machine learning research has achieved large performance gains on a wide range of tasks by expanding the learning target from mean rewards to entire probability distributions of rewards - an approach known as distributional reinforcement learning (RL). The mesolimbic dopamine system is thought to underlie RL in the mammalian brain by updating a representation of mean value in the striatum, but little is known about whether, where, and how neurons in this circuit encode information about higher-order moments of reward distributions. To fill this gap, we used high-density probes (Neuropixels) to acutely record striatal activity from well-trained, water-restricted mice performing a classical conditioning task in which reward mean, reward variance, and stimulus identity were independently manipulated.

M1 receptors interacting with NMDAR enhance delay-related neuronal firing and improve working memory performance.

The recurrent excitatory circuits in dlPFC underlying working memory are known to require activation of glutamatergic NMDA receptors (NMDAR). The neurons in these circuits also rely on acetylcholine to maintain persistent activity, with evidence for actions at both nicotinic α7 receptors and muscarinic M1 receptors (M1R). It is known that nicotinic α7 receptors interact with NMDAR in these circuits, but the interactions between M1R and NMDAR on dlPFC neuronal activity are unknown.

Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex.

Working memory relies on the dorsolateral prefrontal cortex (dlPFC), where microcircuits of pyramidal neurons enable persistent firing in the absence of sensory input, maintaining information through recurrent excitation. This activity relies on acetylcholine, although the molecular mechanisms for this dependence are not thoroughly understood. This study investigated the role of muscarinic M1 receptors (M1Rs) in the dlPFC using iontophoresis coupled with single-unit recordings from aging monkeys with naturally occurring cholinergic depletion.

A Structural Model of the Inactivation Gate of Voltage-Activated Potassium Channels.

After opening, the Shaker voltage-gated potassium (K) channel rapidly inactivates when one of its four N-termini enters and occludes the channel pore. Although it is known that the tip of the N-terminus reaches deep into the central cavity, the conformation adopted by this domain during inactivation and the nature of its interactions with the rest of the channel remain unclear. Here, we use molecular dynamics simulations coupled with electrophysiology experiments to reveal the atomic-scale mechanisms of inactivation.

Seeing structure: Shape skeletons modulate perceived similarity.

An intrinsic part of seeing objects is seeing how similar or different they are relative to one another. This experience requires that objects be mentally represented in a common format over which such comparisons can be carried out. What is that representational format? Objects could be compared in terms of their superficial features (e.