Abstract
Perineuronal nets (PNNs) are highly organized components of the extracellular matrix that surround a subset of mature neurons in the central nervous system. These structures play a critical role in regulating neuronal plasticity, particularly during neurodevelopment. Consistent with this role, their presence is associated with functional and structural stability of the neurons they ensheath. A loss of PNNs in the prefrontal cortex has been suggested to contribute to cognitive impairment in disorders such as schizophrenia. However, the direct consequences of PNN loss in medial prefrontal cortex (mPFC) on cognition has not been demonstrated. Here, we examined behavior after disruption of PNNs in mPFC of Long-Evans rats following injection of the enzyme Chondroitinase ABC (ChABC). Our data show that ChABC-treated animals were impaired on tests of object oddity perception. Performance in the cross-modal object recognition task was not significantly different for ChABC-treated rats, although ChABC-treated rats were not able to perform above chance levels whereas control rats were. ChABC treated animals were not significantly different from controls on tests of prepulse inhibition, set-shifting, reversal learning, or tactile and visual object recognition memory. Posthumous immunohistochemistry confirmed significantly reduced PNNs in mPFC due to ChABC treatment. Moreover, PNN density in the mPFC predicted performance on the oddity task, where higher PNN density was associated with better performance. These findings suggest that PNN loss within the mPFC impairs some aspects of object oddity perception and recognition and that PNNs contribute to cognitive function in young adulthood.
Significance Statement Perineuronal nets (PNNs) are organized components of the extracellular matrix that surround mature central nervous system neurons and are critical for the regulation of neuronal plasticity. A loss of PNNs has been observed in schizophrenia and other central nervous system diseases but the exact functional contribution of these structures or the consequences of their loss are not well understood. Here, we show that targeted degradation of PNNs within the medial prefrontal cortex disrupts performance of some tests of object oddity perception and recognition memory. These findings suggest that PNNs and their loss in CNS diseases may contribute directly to the presentation of cognitive dysfunction.
Footnotes
JGH and IRW have no conflicts to report.
This research was supported by CIHR operating grants #125984 (to JGH) and # 153111 (to JGH and IRW), NSERC Discovery Grants (to JGH and IRW), and a College of Medicine Research Award from the University of Saskatchewan (to JGH).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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