Hippocampal interneurons express a novel form of synaptic plasticity.

Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Neuron (Impact Factor: 15.98). 03/1997; 18(2):295-305. DOI: 10.1016/S0896-6273(00)80269-X
Source: PubMed

ABSTRACT Individual GABAergic interneurons in hippocampus can powerfully inhibit more than a thousand excitatory pyramidal neurons. Therefore, control of interneuron excitability provides control over hippocampal networks. We have identified a novel mechanism in hippocampus that weakens excitatory synapses onto GABAergic interneurons. Following stimulation that elicits long-term potentiation at neighboring synapses onto excitatory cells, excitatory synapses onto inhibitory interneurons undergo a long-term synaptic depression (interneuron LTD; iLTD). Unlike most other forms of hippocampal synaptic plasticity, iLTD is not synapse specific: stimulation of an afferent pathway triggers depression not only of activated synapses but also of inactive excitatory synapses onto the same interneuron. These results suggest that high frequency afferent activity increases hippocampal excitability through a dual mechanism, simultaneously potentiating synapses onto excitatory neurons and depressing synapses onto inhibitory neurons.

  • Annals of Physical and Rehabilitation Medicine 10/2011; 54.
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    ABSTRACT: Matrix metalloproteases (MMP) play a pivotal role in long-term synaptic plasticity, learning, and memory. The roles of different MMP subtypes are emerging, but the proteolytic activity of certain MMPs was shown to support these processes through the structural and functional modification of hippocampal Schaeffer collateral and mossy fiber (MF) synapses. However, certain patterns of synaptic activity are additionally associated with non-synaptic changes, such as the scaling of neuronal excitability. However, the extent to which MMPs affect this process remains unknown. We determined whether MMP activity interferes with excitatory post-synaptic potential EPSP-to-spike (E-S) coupling under conditions of varying synaptic activity. We evoked short- and long-term synaptic plasticity at associational/commissural (A/C) synapses of CA3 pyramidal neurons and simultaneously recorded population spikes (PSs) and EPSPs in acute rat (P30-60) brain slices in the presence of various MMP inhibitors. We found that MMP inhibition significantly reduced E-S coupling and shortened the PS latency associated with 4× 100 Hz stimulation or paired burst activity of MF-CA3 and A/C synapses. Moreover, MMP inhibition interfered with the scaling of amplitude of measured signals during high-frequency trains, thus affecting the induction of long-term potentiation (LTP). The inhibition of L-type voltage-gated calcium channels with 20 µM nifedipine or GABA-A receptors with 1-30 µM picrotoxin did not occlude the effects of MMP inhibitors. However, MMP inhibition significantly reduced the LTP of NMDA receptor-mediated EPSPs. Finally, the analysis of LTP saturation with multiple single (1× 100 Hz) or packed (4× 100 Hz) trains indicated that MMPs support E-S coupling evoked by selected synaptic activity patterns and set the ceiling for tetanically evoked E-S LTP. In conclusion, the activity of MMPs, particularly MMP-3, regulated the magnitude of EPSPs and spike plasticity in the CA3 network and may affect information processing. Our data provide a novel link between MMP activity and neural excitability. Therefore, by limiting the number of firing neurons, MMP may functionally act beyond the synapse. © 2013 Wiley Periodicals, Inc.
    Hippocampus 10/2013; 24(2). · 4.30 Impact Factor
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    ABSTRACT: In pyramidal cells, the induction of spike-dependent plasticity (STDP) follows a simple Hebbian rule in which the order of presynaptic and postsynaptic firing dictates the induction of LTP or LTD. In contrast, cortical fast spiking (FS) interneurons, which control the rate and timing of pyramidal cell firing, reportedly express timing-dependent LTD, but not timing-dependent LTP. Because a mismatch in STDP rules could impact the maintenance of the excitation/inhibition balance, we examined the neuromodulation of STDP in FS cells of mouse visual cortex. We found that stimulation of adrenergic receptors enables the induction of Hebbian bidirectional STDP in FS cells in a manner consistent with a pull-push mechanism previously characterized in pyramidal cells. However, in pyramidal cells, STDP induction depends on NMDA receptors, whereas in FS cells it depends on mGluR5 receptors. We propose that neuromodulators control the polarity of STDP in different synapses in the same manner, and independently of the induction mechanism, by acting downstream in the plasticity cascade. By doing so, neuromodulators may allow coordinated plastic changes in FS and pyramidal cells.
    Journal of Neuroscience 08/2013; 33(32):13171-8. · 6.75 Impact Factor

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