Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation.

Associative learning is crucial for adapting to environmental changes. Interactions among neuronal populations involving the dorso-medial prefrontal cortex (dmPFC) are proposed to regulate associative learning, but how these neuronal populations store and process information about the association remains unclear. Here we developed a pipeline for longitudinal two-photon imaging and computational dissection of neural population activities in male mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC network topology. Using regularized regression methods and graphical modeling, we found that fear conditioning drove dmPFC reorganization to generate a neuronal ensemble encoding conditioned responses (CR) characterized by enhanced internal coactivity, functional connectivity, and association with conditioned stimuli (CS). Importantly, neurons strongly responding to unconditioned stimuli during conditioning subsequently became hubs of this novel associative network for the CS-to-CR transformation. Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on the activity-dependent formation of the hub network within the dmPFC.

Maternal separation decreases the stability of mushroom spines in adult mice somatosensory cortex.

Maternal-separation (MS) is an important model to study the effects of maternal care on infant neuronal development. It has been previously shown that MS contributes to not only structural changes of neurons in the infralimbic cortex but also to significant behavioral changes in adulthood. However, the underlying mechanism of the MS effect on neuronal circuits is not clearly understood. In this study, we studied the effects of MS on the function related to somatosensory cortex (SSC) and spine remodeling in the SSC. We found that MS mice showed hypersensitivity to somatosensory stimulation at post-natal 4, 8 and 12 weeks. MS enhanced the turnover of mushroom-type spines, leading to a decrease of the number of spines in the SSC in young and adult mice observed by using in vivo two-photon laser microscopy imaging. We conclude that MS during development affects the stability of dendritic mushroom spines in the SSC, which possibly produces impairment of the sensory behavior in adult mice.

Neuronal circuit remodeling in the contralateral cortical hemisphere during functional recovery from cerebral infarction.

Recent advances in functional imaging of human brain activity in stroke patients, e.g., functional magnetic resonance imaging, have revealed that cortical hemisphere contralateral to the infarction plays an important role in the recovery process. However, underlying mechanisms occurring in contralateral hemisphere during functional recovery have not been elucidated. We experimentally induced a complete infarction of somatosensory cortex in right hemisphere of mice and examined the neuronal changes in contralateral (left) somatosensory cortex during recovery. Both basal and ipsilateral somatosensory stimuli-evoked neuronal activity in left (intact) hemisphere transiently increased 2 d after stroke, followed by an increase in the turnover rate of usually stable mushroom-type synaptic spines at 1 week, observed by using two-photon imaging in vivo. At 4 weeks after stroke, when functional recovery had occurred, a new pattern of electrical circuit activity in response to somatosensory stimuli was established in intact ipsilateral hemisphere. Thus, the left somatosensory cortex can compensate for the loss of the right somatosensory cortex by remodeling neuronal circuits and establishing new sensory processing. This finding could contribute to establish the effective clinical treatments targeted on the intact hemisphere for the recovery of impaired functions and to achieve better quality of life of patients.