Impaired Cognitive Function after Perineuronal Net Degradation in the Medial Prefrontal Cortex

Abstract

Perineuronal nets (PNNs) are highly organized components of the extracellular matrix that surround a subset of mature neurons in the CNS. 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 (PFC) has been suggested to contribute to cognitive impairment in disorders such as schizophrenia. However, the direct consequences of PNN loss in medial PFC (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 (CMOR) 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 (PPI), set-shifting (SS), 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.

Maternal Immune Activation during Pregnancy Alters the Behavior Profile of Female Offspring of Sprague Dawley Rats

“…Oddity preference and perception have been assessed in several tasks using rats and mice (Bussey et al, 2005; Bartko et al, 2007a,b; Cowell et al, 2010; Cloke et al, 2016; Marks et al, 2018; Paylor et al, 2018); however, to our knowledge this is the first study to assess this oddity task in female rats. Improved understanding of the nature of oddity discrimination is relevant for the successful management of cognitive impairment in conditions such as schizophrenia, a symptom domain highly related to patient functional outcomes (Cloke et al, 2016).…”

“…The testing apparatus was a Y-shaped maze with one start arm and two object arms (10 × 27 cm) made of white corrugated plastic (Fig. 4; Lins et al, 2018; Paylor et al, 2018). A white plastic guillotine-style door separated the start arm from the object arms, and Velcro at the distal end of the object arms fixed objects in place.…”

“…F , both groups failed to display crossmodal recognition memory as novel object exploration was equal to chance; # indicates significant difference from chance exploration (DR = 0, p < 0.05) in a single sample t test. Schematic has been published previously (Lins et al, 2018; Paylor et al, 2018).…”

Learning Induces Transient Upregulation of Brevican in the Auditory Cortex during Consolidation of Long-Term Memories

“…Our data further shows that such protection is restricted to the consolidation of recent, not of remote memories, as protein levels are back to naive levels during LTR. In this line, enzymatic degradation of the ECM has only subtle effects on several forms of initial learning (Paylor et al, 2018), but interferes with the extinction or reversal of recently established memories (Gogolla et al, 2009;Happel et al, 2014). The complex molecular orchestra of cellular and extracellular signals may hence first promote plastic reorganizations and subsequently support their learning-dependent fixation (Donato et al, 2013, Kamigaki andDan, 2017;Ognjanovski et al, 2017).…”

A Further Analysis and Commentary on: Profiling Changes in Cortical Astroglial Cells Following Chronic Stress

“…It is possible, therefore, that a similar process occurs in the PFC; however, in response to chronic rather than acute stress, this becomes maladaptive and leads to decreased plasticity and cognitive flexibility. Indeed, cognitive functions are also impaired when PNNs are not present 16 and of course are a core feature of mood disorders in humans. 7,17 Perineuronal nets surround only a subset of the cortical parvalbumin, somatostatin, and reelin interneuron populations, and functional changes in each of these cell populations have been implicated in major depressive disorder.…”