Laminar pattern of adolescent development changes in working memory neuronal activity

Abstract

Adolescent development is characterized by an improvement in cognitive abilities, such as working memory. Neurophysiological recordings in a non-human primate model of adolescence have revealed changes in neural activity that mirror improvement in behavior, including higher firing rate during the delay intervals of working memory tasks. The laminar distribution of these changes is unknown. By some accounts, persistent activity is more pronounced in superficial layers, so we sought to determine whether changes are most pronounced there. We therefore analyzed neurophysiological recordings from neurons recorded in the young and adult stage, at different cortical depths. Superficial layers exhibited increased baseline firing rate in the adult stage. Unexpectedly, changes in persistent activity were most pronounced in the middle layers. Finally, improved discriminability of stimulus location was most evident in the deeper layers. These results reveal the laminar pattern of neural activity maturation that is associated with cognitive improvement.

New and noteworthy: Structural brain changes are evident during adolescent development particularly in the cortical thickness of the prefrontal cortex, at a time when working memory ability increases markedly. The depth distribution of neurophysiological changes during adolescence is not known. Here we show that neurophysiological changes are not confined to superficial layers, which have most often been implicated in the maintenance of working memory. Contrary to expectations, greatest changes were evident in intermediate layers of the prefrontal cortex.

Figure 1.

A Sequence of events in the Oculomotor Delayed Response (ODR) task. B. Schematic diagram of the monkey brain with approximate location of neuronal recordings in areas 8 and 46 of the dorsolateral prefrontal cortex (dlPFC) highlighted. Abbreviations: AS, arcuate sulcus; PS, principal sulcus.

Figure 2.. Recording depths.

Depths of neurons with significant responses during the task relative to the top of the cortex are shown for the young (A) and adult stage (B). Each horizontal line represents the depth of one neuron. Histograms summarize the depths of neurons in four monkeys in the young and adult stage. Blue horizontal lines indicate the 0, 800 and 1200 μm depths which defined the boundaries for the superficial, middle, and deep groups.

Figure 3.. Firing rate in different depth groups and developmental stages.

A. Average, population peri-stimulus time histogram for neurons that responded to the visual stimulus and were recorded during the ODR task from superficial layer at adult and young stages. Responses are shown for a stimulus in the neuron’s receptive field and aligned to the stimulus onset of each trial. Vertical lines represent stimulus onset and fixation offset. B. As in A, for the mid layer. C. As in A, for the deep layer.

Figure 4.

ROC analysis in each layer. A. Area under ROC curve in successive 100 ms windows is plotted as a function of time during the ODR task, for superficial layer neurons at adult and young stages. B, C. As in A, for the mid layer and deep layer, respectively. D. Percentages of neurons at adult (top) and young (bottom) stages reaching different levels of ROC values at each time point of the ODR task. E, F. As in D, for the mid layer and deep layer, respectively.

Figure 5.

Neuronal tuning in each layer. A. Average activity (and s.e.m.) during the cue period of the ODR task in neurons recorded from superficial layer at adult and young stages. Locations have been rotated, so that the best location of each neuron is represented in location 5. Location 9 is the same as location 1. Solid lines represent the best Gaussian fit of the population average. B, C. As in A, for the mid layer and deep layer, respectively. D. Average activity (and s.e.m.) during the delay period of the ODR task from superficial layer at adult and young stages. E, F. As in D, for the mid layer and deep layer, respectively.