Beyond Sensory Encoding: New Possibilities for Macaque Area MT
Aaron J. Levi, Yuan Zhao, Il Memming Park, and Alexander C. Huk
(see pages 2090–2103)
The middle temporal visual area, also known as area MT, in the rhesus macaque monkey has been well characterized as selectively responding to visual motion and plays an important role in visual perception, but the possibility that it carries out functions beyond simple sensory processing have hardly been considered. Now Levi et al. have probed area MT in two macaques using multineuron electrophysiological recordings and population-level decoding analysis to uncover MT activity separable from sensory discrimination. The researchers used a novel manipulation of the time course of psychophysical weighting while monkeys performed a direction-discrimination task. Specifically, they controlled the temporal weighting strategy, such that stimuli had stronger or weaker motion evidence during early or late phases. The manipulations revealed surprising modulation of sensory responses unrelated to motion detection-related decisions. The authors summarize their findings as showing an inverse relationship between temporal dynamics of behaviors and sensory encoding; a choice-correlated signal that lagged the most relevant stimulus timepoints; and a distinct choice-correlated signal that followed the stimulus. Importantly, the analysis suggested that sensory and nonsensory signals processed in MT were multiplexed by neuronal populations in a way that did not interact in typical feedforward or feedback ways and may have been processed entirely independently from one another. Further, a task in which the subjects made a saccade-based choice did not correlate temporally with stimulus processing or with motor behavior, suggesting a more top-down, cognitive nature of this MT activity. The work opens many new questions about the population coding structure and function of task-related but nonsensory activity in MT.
Gibraltar Barbary macaque image: Wikimedia Commons/RedCoat/CC-BY-SA-2.5.
Distinct Forms of Ethanol Tolerance in Flies
Caleb Larnerd, Pratik Adhikari, Ashley Valdez, Alexander Del Toro, and Fred W. Wolf
(see pages 2210–2220)
While it is not surprising that ethanol use leads to tolerance—a common physiological response to many drugs—what is surprising is that distinct forms of ethanol tolerance—acute, rapid, and chronic—are conserved across species, even in the fly Drosophila melanogaster. But the molecular and circuit underpinnings of these early forms of behavioral plasticity remain largely unknown. This week, Larnerd et al. dissect three forms of ethanol tolerance in flies that depended on the pattern of initial ethanol exposure. Repeating a sedating exposure 4 h later, after the initial dose was metabolized, gave rise to rapid tolerance, which mimics the tolerance seen in humans engaged in binge drinking. Flies chronically exposed to low levels of ethanol developed chronic tolerance, in which flies resisted ethanol sedation, similar to maintenance drinking in people with alcohol use disorder (AUD). In a repeated ethanol exposure, flies received an inebriating, but not sedating, dose of ethanol for 20 min/d for 4 d. That produced repeated tolerance, characterized by reduced sensitivity and a slight aversion to ethanol. The researchers examined the molecular roots of this neural plasticity, focusing on immediate early gene transcription factors and the structure of chromatin. Interestingly, the three forms of tolerance were distinct, each inducing different factors. The researchers traced plasticity encoding to histone deacetylation by multiple histone deacetylases including the sirtuin Sirt1, which promoted rapid tolerance but inhibited chronic tolerance. They further distinguished the forms of tolerance anatomically by mapping them to distinct circuits of the mushroom body, the learning and memory center in the fly brain. Critically, the researchers found that rapid and chronic tolerance are molecularly and temporally similar to intermediate-term and long-term memory, respectively. However, ethanol appears to create a unique form of long-term memory. This description of multiple, distinct forms of ethanol tolerance point to complex neural plasticity that forms long-term memory-like states, which may form a basis for the development of AUD.
Footnotes
This Week in The Journal was written by Stephani Sutherland
