Dr Andrei Rozov

The efficacy of synaptic transmission in neuronal circuits is not constant but varies with the rate of action potentials in presynaptic neurons. During a train of action potentials, the amplitudes of successively evoked postsynaptic potentials (PSPs) either increase (facilitate) or decrease (depress). An increase or decrease in the probability of transmitter release caused by the effects of successive action potentials in the presynaptic terminal are postulated to underlie short-term modification of PSPs. Alternatively, biophysical properties of postsynaptic ligand-gated ion channels can be changed upon repetitive synaptic activity, increasing or decreasing ionic current through these channels and the pattern of PSPs.

Short-term plasticity and endogenous Ca2+ buffers

Previously we have suggested a novel mechanism by which facilitation can arise from local and partial saturation of Ca2+ buffers. Such a mechanism might account for facilitation in those neurons that have an increased endogenous buffer capacity, like most of GABAergic inhibitory interneurons. Indeed, we found that saturation of calbindin (a fast endogenous Ca2+ buffer) underlies facilitation in GABAergic terminals as well as in hippocampal mossy fiber terminals. Another candidate for the role of “key player “ in short-term synaptic plasticity might be calretinin. Calretinin is a Ca2+-binding protein with four cooperative binding sites and one independent binding site. It has been shown that calretinin can work either as a “slow” or “fast” buffer depending on Ca2+ concentration and occupancy of the binding sites. Presynaptic Ca2+ concentration is strongly dependent on neuronal firing rate. In this scenario in non-active neurons calretinin will behave as a slow buffer, but following a burst of activity calretinin will switch to the fast binding mode. Taken together, the dual nature of calretinin Ca2+ binding allows neurons to code the history of neuronal activity.

GABAA receptor – postsynaptic target for direct cannabinoid modulation

Cannabinoids are known to regulate inhibitory synaptic transmission via activation of presynaptic G-protein-coupled cannabinoid CB1 receptors (CB1Rs). However recently we found that cannabinoids can suppress inhibitory synaptic transmission in synapses lacking the CB1R. Whole-cell recordings from fast-spiking interneuron to pyramidal neuron pairs, in neocortical brain slices from rats and CB1R knockout mice, show that both exogenously applied and endogenously released cannabinoids suppress GABAA receptor (GABAAR) mediated inhibitory synaptic transmission, independent of CB1R activation. This inhibition is likely to be caused by the direct interaction of cannabinoids with postsynaptic GABAARs, since we show that cannabinoids reduce the amplitude and modulate the kinetics of currents mediated by both recombinant and native GABAARs in isolated cells. Finally, we show that CB1R-independent suppression of inhibition by (endo)cannabinoids reduces the influence of FS interneurons on the action potential firing of pyramidal cells. However, it remains unclear whether sensitivity to (endo)cannabinoids depends on GABAAR subunit composition. In this respect it would be interesting to test the effects of cannabinoids at different synapses, as well as on tonic inhibition.

Rozov A, Burnashev N, Sakmann B, Neher E. (2001) Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics. J Physiol. 531: 807-826

Mack V, Burnashev N, Kaiser KM, Rozov A, Jensen V, Hvalby O, Seeburg PH, Sakmann B, Sprengel R. (2001) Conditional restoration of hippocampal synaptic potentiation in Glur-A-deficient mice. Science. 292: 2501-2504.

Hormuzdi SG, Pais I, LeBeau FE, Towers SK, Rozov A, Buhl EH, Whittington MA, Monyer H. (2001) Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron. 31: 487-495.

Rozov A, Jerecic J, Sakmann B, Burnashev N. (2001) AMPA receptor channels with long-lasting desensitization in bipolar interneurons contribute to synaptic depression in a novel feedback circuit in layer 2/3 of rat neocortex. J Neurosci. 21: 8062-8071.

Sansig G, Bushell TJ, Clarke VR, Rozov A, Burnashev N, Portet C, Gasparini F, Schmutz M, Klebs K, Shigemoto R, Flor PJ, Kuhn R, Knoepfel T, Schroeder M, Hampson DR, Collett VJ, Zhang C, Duvoisin RM, Collingridge GL, van Der Putten H. (2001) Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. J Neurosci. 21: 8734-8745.

Meyer AH, Katona I, Blatow M, Rozov A, Monyer H. (2002) In vivo labeling of parvalbumin-positive interneurons and analysis of electrical coupling in identified neurons. J Neurosci. 22: 7055-7064.

Blatow M, Caputi A, Burnashev N, Monyer H, Rozov A. (2003) Ca2+ buffer saturation underlies paired pulse facilitation in calbindin-D28k-containing terminals. Neuron. 38:79-88.

Rozov A, Blatow M, Katona I, Hormuzdi SG, Meyer AH, Whittington MA, Caputi A, Monyer H. (2003) A novel network of multipolar bursting interneurons generates theta frequency oscillations in neocortex.
Neuron. 38: 805-817.

Jensen V, Kaiser KM, Borchardt T, Adelmann G, Rozov A, Burnashev N, Brix C, Frotscher M, Andersen P, Hvalby O, Sakmann B, Seeburg PH, Sprengel R. (2003) A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A. J Physiol. 553: 843-856.

Schulz TW, Nakagawa T, Licznerski P, Pawlak V, Kolleker A, Rozov A, Kim J, Dittgen T, Kohr G, Sheng M, Seeburg PH, Osten P. (2004) Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. J Neurosci. 24:8584-8594.

Watanabe J, Rozov A, Wollmuth LP. (2005) Target-specific regulation of synaptic amplitudes in the neocortex.J Neurosci. 25: 1024-1033.

Fuchs EC, Zivkovic AR, Cunningham MO, Middleton S, Lebeau FE, Bannerman DM, Rozov A, Whittington MA, Traub RD, Rawlins JN, Monyer H. (2007) Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior.
Neuron. 53: 591-604.

Von Engelhardt J, Eliava M, Meyer AH., Rozov A, Monyer H. (2007) Functional characterization of intrinsic cholinergic interneurons in the cortex. J Neurosci. 27: 5633-5642.

Celikel T, Marx V, Freudenberg F, Resnik E, Zivkovic A, Hasan MT, Plicznerski P, Osten P, Rozov A, Seeburg PH, Schwarz MK (2007) Sustained Homer1a expression impairs LTP, spatial working memory but not spatial reference memory. Front Neurosci.. 1: 97-110

Rozov A., Caputi A. Blatow M, Monyer H. (2008) Two Calretinin-positive GABAergic cell populations in layer II/III of the mouse neocortex provide different forms of disinhibition. Cereb Cortex.