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Diverse impact of acute and long-term extracellular proteolytic activity on plasticity of neuronal excitability.

Wójtowicz T, Brzdąk P, Mozrzymas JW - Front Cell Neurosci (2015)

Bottom Line: With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses.Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function.Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic backpropagation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University Wroclaw, Poland.

ABSTRACT
Learning and memory require alteration in number and strength of existing synaptic connections. Extracellular proteolysis within the synapses has been shown to play a pivotal role in synaptic plasticity by determining synapse structure, function, and number. Although synaptic plasticity of excitatory synapses is generally acknowledged to play a crucial role in formation of memory traces, some components of neural plasticity are reflected by nonsynaptic changes. Since information in neural networks is ultimately conveyed with action potentials, scaling of neuronal excitability could significantly enhance or dampen the outcome of dendritic integration, boost neuronal information storage capacity and ultimately learning. However, the underlying mechanism is poorly understood. With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses. Here, we review the most recent studies addressing the impact of extracellular proteolysis on plasticity of neuronal excitability and discuss how enzymatic activity may alter input-output/transfer function of neurons, supporting cognitive processes. Interestingly, extracellular proteolysis may alter intrinsic neuronal excitability and excitation/inhibition balance both rapidly (time of minutes to hours) and in long-term window. Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function. Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic backpropagation.

No MeSH data available.


Related in: MedlinePlus

Summary of the known role of several proteases in rapid (requiring minutes to hours) changes in EPSP-to-spike (E-S) potentiation and/or neuronal spiking. A cartoon indicates the putative regions of CA1 pyramidal neuron where extracellular proteolysis may affect intrinsic neuronal excitability and E-S potentiation via (a) cleavage of extracellular matrix (ECM) constituents and modulation of ion channels; (b) modulation of inhibitory inputs efficacy (see text for details). The list of known targets of extracellular proteolysis and putative regions of action is listed in the table. N.D.- no data available.
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Figure 1: Summary of the known role of several proteases in rapid (requiring minutes to hours) changes in EPSP-to-spike (E-S) potentiation and/or neuronal spiking. A cartoon indicates the putative regions of CA1 pyramidal neuron where extracellular proteolysis may affect intrinsic neuronal excitability and E-S potentiation via (a) cleavage of extracellular matrix (ECM) constituents and modulation of ion channels; (b) modulation of inhibitory inputs efficacy (see text for details). The list of known targets of extracellular proteolysis and putative regions of action is listed in the table. N.D.- no data available.

Mentions: Low levels of several proteases are normally present in hippocampus and include for instance trypsin (Koshikawa et al., 1998), neuropsin (Tomimatsu et al., 2002), neurotrypsin (motopsin, Mitsui et al., 2007), tissue plasminogen activator (tPA; Pawlak and Strickland, 2002), thrombin (Rohatgi et al., 2004) and MMPs (e.g., MMP-2–9, Szklarczyk et al., 2002; Wiera et al., 2012). Activity of these serine proteases and metalloproteases was shown to be crucial for synaptic plasticity and memory (reviewed in Tomimatsu et al., 2002; Shiosaka, 2004; Sonderegger and Matsumoto-Miyai, 2014). Following enhanced neuronal activity such as that occurring during formation of memory traces, proteases may be rapidly released and activated in extracellular space and support synaptic plasticity. For instance, tPA is rapidly secreted following membrane depolarization and Ca2+ entry (Gualandris et al., 1996; Parmer et al., 1997; Baranes et al., 1998), while activity of protease neuropsin was shown to rapidly increase as early as 5 min following neuronal activity and activation of NMDARs (Matsumoto-Miyai et al., 2003). Similarly, neurotrypsin may be exocytosed as early as 30 s–2 min post stimulation of neurons with KCl and then removed within several minutes (Frischknecht et al., 2008). In addition, matrix metalloprotease 9 (MMP-9) was shown to follow vesicular release (Sbai et al., 2008) and its activity was detected as early as 5 min following stimulation of cultured neurons with glutamate or blockers of inhibitory transmission (Michaluk et al., 2007). More recently, rapid release and enhanced activity of MMP-9 in the synapse was shown to occur as early as 5–10 min following stimulation (Dziembowska et al., 2012; Stawarski et al., 2014). Thus, taken that use-dependent plasticity of intrinsic excitability has been reported in numerous regions of the brain, including hippocampus, cerebellum and neocortex (see for reviews Daoudal and Debanne, 2003; Zhang and Linden, 2003) the question arises to what extent proteolytic activity in extracellular space could support these processes? In the following sections, we discuss literature related to proteolysis-mediated and activity-dependent changes in neuronal excitability and E-S potentiation (see also Figure 1).


Diverse impact of acute and long-term extracellular proteolytic activity on plasticity of neuronal excitability.

Wójtowicz T, Brzdąk P, Mozrzymas JW - Front Cell Neurosci (2015)

Summary of the known role of several proteases in rapid (requiring minutes to hours) changes in EPSP-to-spike (E-S) potentiation and/or neuronal spiking. A cartoon indicates the putative regions of CA1 pyramidal neuron where extracellular proteolysis may affect intrinsic neuronal excitability and E-S potentiation via (a) cleavage of extracellular matrix (ECM) constituents and modulation of ion channels; (b) modulation of inhibitory inputs efficacy (see text for details). The list of known targets of extracellular proteolysis and putative regions of action is listed in the table. N.D.- no data available.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530619&req=5

Figure 1: Summary of the known role of several proteases in rapid (requiring minutes to hours) changes in EPSP-to-spike (E-S) potentiation and/or neuronal spiking. A cartoon indicates the putative regions of CA1 pyramidal neuron where extracellular proteolysis may affect intrinsic neuronal excitability and E-S potentiation via (a) cleavage of extracellular matrix (ECM) constituents and modulation of ion channels; (b) modulation of inhibitory inputs efficacy (see text for details). The list of known targets of extracellular proteolysis and putative regions of action is listed in the table. N.D.- no data available.
Mentions: Low levels of several proteases are normally present in hippocampus and include for instance trypsin (Koshikawa et al., 1998), neuropsin (Tomimatsu et al., 2002), neurotrypsin (motopsin, Mitsui et al., 2007), tissue plasminogen activator (tPA; Pawlak and Strickland, 2002), thrombin (Rohatgi et al., 2004) and MMPs (e.g., MMP-2–9, Szklarczyk et al., 2002; Wiera et al., 2012). Activity of these serine proteases and metalloproteases was shown to be crucial for synaptic plasticity and memory (reviewed in Tomimatsu et al., 2002; Shiosaka, 2004; Sonderegger and Matsumoto-Miyai, 2014). Following enhanced neuronal activity such as that occurring during formation of memory traces, proteases may be rapidly released and activated in extracellular space and support synaptic plasticity. For instance, tPA is rapidly secreted following membrane depolarization and Ca2+ entry (Gualandris et al., 1996; Parmer et al., 1997; Baranes et al., 1998), while activity of protease neuropsin was shown to rapidly increase as early as 5 min following neuronal activity and activation of NMDARs (Matsumoto-Miyai et al., 2003). Similarly, neurotrypsin may be exocytosed as early as 30 s–2 min post stimulation of neurons with KCl and then removed within several minutes (Frischknecht et al., 2008). In addition, matrix metalloprotease 9 (MMP-9) was shown to follow vesicular release (Sbai et al., 2008) and its activity was detected as early as 5 min following stimulation of cultured neurons with glutamate or blockers of inhibitory transmission (Michaluk et al., 2007). More recently, rapid release and enhanced activity of MMP-9 in the synapse was shown to occur as early as 5–10 min following stimulation (Dziembowska et al., 2012; Stawarski et al., 2014). Thus, taken that use-dependent plasticity of intrinsic excitability has been reported in numerous regions of the brain, including hippocampus, cerebellum and neocortex (see for reviews Daoudal and Debanne, 2003; Zhang and Linden, 2003) the question arises to what extent proteolytic activity in extracellular space could support these processes? In the following sections, we discuss literature related to proteolysis-mediated and activity-dependent changes in neuronal excitability and E-S potentiation (see also Figure 1).

Bottom Line: With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses.Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function.Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic backpropagation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University Wroclaw, Poland.

ABSTRACT
Learning and memory require alteration in number and strength of existing synaptic connections. Extracellular proteolysis within the synapses has been shown to play a pivotal role in synaptic plasticity by determining synapse structure, function, and number. Although synaptic plasticity of excitatory synapses is generally acknowledged to play a crucial role in formation of memory traces, some components of neural plasticity are reflected by nonsynaptic changes. Since information in neural networks is ultimately conveyed with action potentials, scaling of neuronal excitability could significantly enhance or dampen the outcome of dendritic integration, boost neuronal information storage capacity and ultimately learning. However, the underlying mechanism is poorly understood. With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses. Here, we review the most recent studies addressing the impact of extracellular proteolysis on plasticity of neuronal excitability and discuss how enzymatic activity may alter input-output/transfer function of neurons, supporting cognitive processes. Interestingly, extracellular proteolysis may alter intrinsic neuronal excitability and excitation/inhibition balance both rapidly (time of minutes to hours) and in long-term window. Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function. Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic backpropagation.

No MeSH data available.


Related in: MedlinePlus