scholarly journals Emergence of Non-Linear Mixed Selectivity in Prefrontal Cortex after Training

2020 ◽  
Author(s):  
Wenhao Dang ◽  
Russell J. Jaffe ◽  
Xue-Lian Qi ◽  
Christos Constantinidis

ABSTRACTNeurons in the prefrontal cortex (PFC) are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neuron’s selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing location and shape combinations, does not increase the degree of NMS for stimulus shape with other task variables. Lastly, in contrast to the previous studies, we did not find evidence that NMS is predictive of task performance. Our results thus provide critical insights on the representation of stimuli and task information in neuronal populations, which may pave the way to a greater understanding of neural selectivity in working memory.SIGNIFICANCE STATEMENTHow multiple types of information are represented in working memory remains a complex computational problem. It has been hypothesized that nonlinear mixed selectivity allows neurons to efficiently encode multiple stimuli in different contexts, after subjects have been trained in complex tasks. Our analysis of prefrontal recordings obtained before and after training monkeys to perform working memory tasks only partially agreed with this prediction, in that nonlinear mixed selectivity emerged for spatial but not shape information, and mostly in mid-dorsal PFC. Nonlinear mixed selectivity also displayed little modulation across either task complexity or correct performance. These results point to other mechanisms, in addition to nonlinear mixed selectivity, to represent complex information about stimulus and context in neuronal activity.


Author(s):  
Megan Roussy ◽  
Rogelio Luna ◽  
Lyndon Duong ◽  
Benjamin Corrigan ◽  
Roberto A. Gulli ◽  
...  

AbstractKetamine is a dissociative anesthetic drug, which has more recently emerged as a rapid-acting antidepressant. When acutely administered at subanesthetic doses, ketamine causes cognitive deficits like those observed in patients with schizophrenia, including impaired working memory. Although these effects have been linked to ketamine’s action as an N-methyl-D-aspartate receptor antagonist, it is unclear how synaptic alterations translate into changes in brain microcircuit function that ultimately influence cognition. Here, we administered ketamine to rhesus monkeys during a spatial working memory task set in a naturalistic virtual environment. Ketamine induced transient working memory deficits while sparing perceptual and motor skills. Working memory deficits were accompanied by decreased responses of fast spiking inhibitory interneurons and increased responses of broad spiking excitatory neurons in the lateral prefrontal cortex. This translated into a decrease in neuronal tuning and information encoded by neuronal populations about remembered locations. Our results demonstrate that ketamine differentially affects neuronal types in the neocortex; thus, it perturbs the excitation inhibition balance within prefrontal microcircuits and ultimately leads to selective working memory deficits.



2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aishwarya Parthasarathy ◽  
Cheng Tang ◽  
Roger Herikstad ◽  
Loong Fah Cheong ◽  
Shih-Cheng Yen ◽  
...  

Abstract Maintenance of working memory is thought to involve the activity of prefrontal neuronal populations with strong recurrent connections. However, it was recently shown that distractors evoke a morphing of the prefrontal population code, even when memories are maintained throughout the delay. How can a morphing code maintain time-invariant memory information? We hypothesized that dynamic prefrontal activity contains time-invariant memory information within a subspace of neural activity. Using an optimization algorithm, we found a low-dimensional subspace that contains time-invariant memory information. This information was reduced in trials where the animals made errors in the task, and was also found in periods of the trial not used to find the subspace. A bump attractor model replicated these properties, and provided predictions that were confirmed in the neural data. Our results suggest that the high-dimensional responses of prefrontal cortex contain subspaces where different types of information can be simultaneously encoded with minimal interference.



2017 ◽  
Author(s):  
Samuel S. McAfee ◽  
Yu Liu ◽  
Roy V. Sillitoe ◽  
Detlef H. Heck

AbstractThe cerebellum has long been recognized for its role in tasks involving precise timing, particularly the temporal coordination of movements. Here we asked whether cerebellar might be involved in the temporal coordination of the phases of neuronal oscillations in the medial prefrontal cortex (mPFC) and dorsal hippocampus CA1 region (CA1). These two structures and the cerebellum are jointly involved in spatial working memory. The phases of oscillations in the mPFC and CA1 have been shown to reach a stable alignment (coherence) during the decision making process in a spatial working memory task. Here we report that PC simple spike activity in the cerebellar lobulus simplex in awake, head-fixed mice represents specific phase differences between oscillations in the mPFC and CA1. Most PCs represented phase differences in more than one the conventional frequency bands (delta, theta, beta and gamma). Between the 32 PCs analyzed here, phase differences in all frequency bands were represented. PCs representing phase differences in the theta and low gamma bands showed significant population preference for mPFC phase leading CA1 phase. These findings support the possibility of a cerebellar involvement in the temporal coordination of phase relationships between oscillations in the mPFC and CA1.



eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Claudia Böhm ◽  
Albert K Lee

The prefrontal cortex (PFC)’s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate – after distractions and a delay – to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form – that is differences in the rate, sequence, phase, or covariance of firing. This suggests that such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.



Author(s):  
Vasiliki Stavroulaki ◽  
Vasileios Ioakeimidis ◽  
Xanthippi Konstantoudaki ◽  
Kyriaki Sidiropoulou


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