Disruption of rat deep cerebellar perineuronal net alters eyeblink conditioning and neuronal electrophysiology

O'Dell, Deidre E.; Schreurs, Bernard G.; Smith-Bell, Carrie A.; Wang, Desheng

doi:10.1016/j.nlm.2020.107358

Cited by 4 publications

(16 citation statements)

References 111 publications

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“…This is consistent with reduced firing of these neurons, an increased number of inhibitory terminals and reduced excitatory terminals [ 31 ], and greater inhibition of DCN neurons [ 70 ]. The increased acquisition is in contrast to another study [ 78 ] that showed a reduced conditioned response and no change during extinction. The differences between studies may be due to differences in species, strength of the unconditioned stimulus, or the method of ChABC delivery.…”

Section: Extracellular Matrix Biologycontrasting

confidence: 99%

The extracellular matrix and perineuronal nets in memory

et al. 2022

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All components of the CNS are surrounded by a diffuse extracellular matrix (ECM) containing chondroitin sulphate proteoglycans (CSPGs), heparan sulphate proteoglycans (HSPGs), hyaluronan, various glycoproteins including tenascins and thrombospondin, and many other molecules that are secreted into the ECM and bind to ECM components. In addition, some neurons, particularly inhibitory GABAergic parvalbumin-positive (PV) interneurons, are surrounded by a more condensed cartilage-like ECM called perineuronal nets (PNNs). PNNs surround the soma and proximal dendrites as net-like structures that surround the synapses. Attention has focused on the role of PNNs in the control of plasticity, but it is now clear that PNNs also play an important part in the modulation of memory. In this review we summarize the role of the ECM, particularly the PNNs, in the control of various types of memory and their participation in memory pathology. PNNs are now being considered as a target for the treatment of impaired memory. There are many potential treatment targets in PNNs, mainly through modulation of the sulphation, binding, and production of the various CSPGs that they contain or through digestion of their sulphated glycosaminoglycans.

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Section: Extracellular Matrix Biologycontrasting

confidence: 99%

The extracellular matrix and perineuronal nets in memory

et al. 2022

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“…Electrophysiological measurements indicated that WFA labeling did not affect firing rates (p ¼ 0.6456), action potential threshold (p ¼ 0.5305), action potential half width (p ¼ 0.4920), or membrane resistance (p ¼ 0.8377). Notably, other studies have used WFA for labeling PNNs during electrophysiological recordings in acute slices and cultures and did not report any methodological artifacts; 9,32 further justifying the approach presented here. In vivo, we found that while the detected calcium transient event rate in the barrel cortex was similar in PV þ ∕PNN þ and PV þ ∕PNN − interneurons, the mean and median area under the curve (AUC) of PV þ ∕PNN þ were larger [p < 0.01 and p < 0.05, respectively; Fig.…”

Section: Resultssupporting

confidence: 51%

Longitudinal in vivo imaging of perineuronal nets

et al. 2023

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Significance: Perineuronal nets (PNNs) are extracellular matrix structures implicated in learning, memory, information processing, synaptic plasticity, and neuroprotection. However, our understanding of mechanisms governing the evidently important contribution of PNNs to central nervous system function is lacking. A primary cause for this gap of knowledge is the absence of direct experimental tools to study their role in vivo.Aim: We introduce a robust approach for quantitative longitudinal imaging of PNNs in brains of awake mice at subcellular resolution.Approach: We label PNNs in vivo with commercially available compounds and monitor their dynamics with two-photon imaging.Results: Using our approach, we show that it is possible to longitudinally follow the same PNNs in vivo while monitoring degradation and reconstitution of PNNs. We demonstrate the compatibility of our method to simultaneously monitor neuronal calcium dynamics in vivo and compare the activity of neurons with and without PNNs. Conclusion:Our approach is tailored for studying the intricate role of PNNs in vivo, while paving the road for elucidating their role in different neuropathological conditions.

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“…This highlights the importance of the current study and the protocol established for an accessible experimental methodology to further investigate olivocerebellar activity in behaving animals. The olivocerebellar circuitry has so far been studied largely using a limited number of behavioral paradigms, such as the forelimb aiming task [ 46 ], the footprint pattern [ 24 ], and eye blink conditions [ 47 ]. Here, we utilized an open field environment as the behavioral paradigm to study CF Ca 2+ signals that reflect spontaneous independent movement, but our methods can be easily adapted to investigate a diversity of behavioral paradigms.…”

Section: Discussionmentioning

confidence: 99%

Optical Fiber-Based Recording of Climbing Fiber Ca2+ Signals in Freely Behaving Mice

Tang

Xue

Wang

et al. 2022

Biology

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The olivocerebellar circuitry is important to convey both motor and non-motor information from the inferior olive (IO) to the cerebellar cortex. Several methods are currently established to observe the dynamics of the olivocerebellar circuitry, largely by recording the complex spike activity of cerebellar Purkinje cells; however, these techniques can be technically challenging to apply in vivo and are not always possible in freely behaving animals. Here, we developed a method for the direct, accessible, and robust recording of climbing fiber (CF) Ca2+ signals based on optical fiber photometry. We first verified the IO stereotactic coordinates and the organization of contralateral CF projections using tracing techniques and then injected Ca2+ indicators optimized for axonal labeling, followed by optical fiber-based recordings. We demonstrated this method by recording CF Ca2+ signals in lobule IV/V of the cerebellar vermis, comparing the resulting signals in freely moving mice. We found various movement-evoked CF Ca2+ signals, but the onset of exploratory-like behaviors, including rearing and tiptoe standing, was highly synchronous with recorded CF activity. Thus, we have successfully established a robust and accessible method to record the CF Ca2+ signals in freely behaving mice, which will extend the toolbox for studying cerebellar function and related disorders.

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Disruption of rat deep cerebellar perineuronal net alters eyeblink conditioning and neuronal electrophysiology

Cited by 4 publications

References 111 publications

The extracellular matrix and perineuronal nets in memory

The extracellular matrix and perineuronal nets in memory

Longitudinal in vivo imaging of perineuronal nets

Optical Fiber-Based Recording of Climbing Fiber Ca2+ Signals in Freely Behaving Mice

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