Stimulation Pattern-Dependent Plasticity at Hippocampal CCK-Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.Long-term plasticity plays an important role in the functional construction of neuronal networks. While anatomical wiring provides essential hardware for brain function, activity-dependent plasticity works as an adjustable software interface allowing sensory induced modification of transmission efficacy at given synaptic connections. In contrast to the vast majority of excitatory synapses, at distinct types of inhibitory GABAergic connections, the link between the pattern of activity and the subsequent change of synaptic strength has not been well characterized. Here, we examined frequency and stimulation pattern dependence in long-term synaptic depression at CCK+/CB1R inhibitory perisomatic synapses in the hippocampal CA1 region, and we found that successful LTD induction depends on the pattern of stimulation rather than the number of stimuli

Selective Extracellular Stimulation of Pharmacologically Distinct CCK/CB1R Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.During prolonged whole cell recording, the intracellular contents are progressively dialyzed with the pipette solution; this often leads to significant changes in synaptic efficacy. To overcome this problem, we developed an approach allowing reliable extracellular stimulation of perisomatic synapses formed by CCK+/CB1+ interneurons onto CA1 pyramidal cells. Functional identification of this input was based on the unique features of CCK+/CB1+ terminals: long-lasting asynchronous transmitter release following high-frequency stimulation and exclusive expression of CB1R. Asynchronous release was used as an indication of proper positioning of the theta glass stimulation pipettes. We found that all extracellularly stimulated inputs with characteristic asynchronous release undergo robust DSI in response to 5-s depolarization and could also be almost entirely blocked by application of the CB1R agonist CP55940, which were similar to the data obtained with paired recordings from connected CB1+ and CA1 pyramidal cells. Thus, we have developed an approach allowing the selective and reliable extracellular stimulation of a subtype of hippocampal perisomatic inhibitory synapses

GABABR-dependent long-term depression at hippocampal synapses between CB1-positive interneurons and CA1 pyramidal cells

© 2016 Jappy, Valiullina, Draguhn and Rozov. Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1 Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAb receptors. We also showed that LTD at this synaptic connection involves GABAbR- dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect. CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation

GABA<inf>B</inf>R-dependent long-term depression at hippocampal synapses between CB1-positive interneurons and CA1 pyramidal cells

© 2016 Jappy, Valiullina, Draguhn and Rozov.Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1 Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAb receptors. We also showed that LTD at this synaptic connection involves GABAbR- dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect. CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation

Differential surface density and modulatory effects of presynaptic GABAB receptors in hippocampal cholecystokinin and parvalbumin basket cells

The perisomatic domain of cortical neurons is under the control of two major GABAergic inhibitory interneuron types: regular-spiking cholecystokinin (CCK) basket cells (BCs) and fast-spiking parvalbumin (PV) BCs. CCK and PV BCs are different not only in their intrinsic physiological, anatomical and molecular characteristics, but also in their presynaptic modulation of their synaptic output. Most GABAergic terminals are known to contain GABAB receptors (GABABR), but their role in presynaptic inhibition and surface expression have not been comparatively characterized in the two BC types. To address this, we performed whole-cell recordings from CCK and PV BCs and postsynaptic pyramidal cells (PCs), as well as freeze-fracture replica-based quantitative immunogold electron microscopy of their synapses in the rat hippocampal CA1 area. Our results demonstrate that while both CCK and PV BCs contain functional presynaptic GABABRs, their modulatory effects and relative abundance are markedly different at these two synapses: GABA release is dramatically inhibited by the agonist baclofen at CCK BC synapses, whereas a moderate reduction in inhibitory transmission is observed at PV BC synapses. Furthermore, GABABR activation has divergent effects on synaptic dynamics: paired-pulse depression (PPD) is enhanced at CCK BC synapses, but abolished at PV BC synapses. Consistent with the quantitative differences in presynaptic inhibition, virtually all CCK BC terminals were found to contain GABABRs at high densities, but only 40% of PV BC axon terminals contain GABABRs at detectable levels. These findings add to an increasing list of differences between these two interneuron types, with implications for their network functions

Functional analysis of recombinant channels in host cells using a fast agonist application system

© Springer Science+Business Media LLC 2017. A reduced recombinant system provides a unique opportunity to study the biophysical properties of NMDAR channels with known subunit compositions, by using a point mutation approach to analyze the structural determinants of receptor function (Wollmuth and Sobolevsky, Trends Neurosci 27:321–328, 2004). However, in addition to the well-developed repertoire of molecular biological techniques, these types of studies also require electrophysiological methods that allow a wide range of receptor activation protocols that can adequately assess desensitization, inactivation, ion permeability, and other properties of the channels. Currently, one of the most well-developed techniques suitable for addressing these issues is use of the fast agonist application system for rapid activation of ligand gated ion-channels (Colquhoun et al., J Physiol 458:261–287, 1992; Jonas and Sakmann, J Physiol 455:143–171, 1992)

Functional analysis of recombinant channels in host cells using a fast agonist application system

© Springer Science+Business Media LLC 2017. A reduced recombinant system provides a unique opportunity to study the biophysical properties of NMDAR channels with known subunit compositions, by using a point mutation approach to analyze the structural determinants of receptor function (Wollmuth and Sobolevsky, Trends Neurosci 27:321–328, 2004). However, in addition to the well-developed repertoire of molecular biological techniques, these types of studies also require electrophysiological methods that allow a wide range of receptor activation protocols that can adequately assess desensitization, inactivation, ion permeability, and other properties of the channels. Currently, one of the most well-developed techniques suitable for addressing these issues is use of the fast agonist application system for rapid activation of ligand gated ion-channels (Colquhoun et al., J Physiol 458:261–287, 1992; Jonas and Sakmann, J Physiol 455:143–171, 1992)

Stimulation Pattern-Dependent Plasticity at Hippocampal CCK-Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.Long-term plasticity plays an important role in the functional construction of neuronal networks. While anatomical wiring provides essential hardware for brain function, activity-dependent plasticity works as an adjustable software interface allowing sensory induced modification of transmission efficacy at given synaptic connections. In contrast to the vast majority of excitatory synapses, at distinct types of inhibitory GABAergic connections, the link between the pattern of activity and the subsequent change of synaptic strength has not been well characterized. Here, we examined frequency and stimulation pattern dependence in long-term synaptic depression at CCK+/CB1R inhibitory perisomatic synapses in the hippocampal CA1 region, and we found that successful LTD induction depends on the pattern of stimulation rather than the number of stimuli

Stimulation Pattern-Dependent Plasticity at Hippocampal CCK-Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.Long-term plasticity plays an important role in the functional construction of neuronal networks. While anatomical wiring provides essential hardware for brain function, activity-dependent plasticity works as an adjustable software interface allowing sensory induced modification of transmission efficacy at given synaptic connections. In contrast to the vast majority of excitatory synapses, at distinct types of inhibitory GABAergic connections, the link between the pattern of activity and the subsequent change of synaptic strength has not been well characterized. Here, we examined frequency and stimulation pattern dependence in long-term synaptic depression at CCK+/CB1R inhibitory perisomatic synapses in the hippocampal CA1 region, and we found that successful LTD induction depends on the pattern of stimulation rather than the number of stimuli