Control of intrinsic and integrative properties by background synaptic bombardment in biological and hybrid networks. Thierry Bal 1 , Damien Debay 1 , Jakob Wolfart 1 , Mathilde Badoual 1 , Zuzanna Piwkowska 1 , Alain Destexhe 1 , Gwendal Le Masson 2 (1) UNIC, CNRS UPR 2191, Inst. A. Fessard, Gif-sur-Yvette, France. (2) EPI INSERM 9914, Institut F. Magendie, Univ. Bordeaux 2, France The spike response of thalamic and cortical neurons to synaptic inputs is influenced by intrinsic membrane properties and by plasticity processes but may also be shaped by the “conductance state” of the neuron [1]. This conductance state is determined by a robust and ever changing background level of transmitter release resulting from local synaptic interactions and by the overall state of the network, from sleep to waking and attentiveness. We examine these properties at the cellular level using slices that generate spontaneous population activity [2] and using hybrid technology based on dynamic clamp (Fig.1) [3, 4]. Thalamocortical neurons relay sensory information to the cortex and receive synaptic feedback, the function of which is unclear. We studied the influence of artificial synaptic bombardment, mimicking the cortical feedback (Fig. 2C), on the response of thalamocortical cells by injecting stochastically fluctuating mixed excitatory/inhibitory background conductances (Fig. 2A). The conductance background modulated the input/output gain, increasing the sensitivity to small inputs (Fig. 2C), and reduced the influence of T-type calcium channels. In addition, it increased the occurrence of burst firing at resting potentials (not shown). Therefore, gain modulation via synaptic background could be a mechanism by which corticothalamic feedback dynamically regulates the thalamic relay of sensory information. Furthermore, our results suggest that the intrinsic response behavior of neurons is substantially altered during high-conductance states. Finally, we compare these results to similar data obtained in cortical networks. Within the cerebral cortex, neurons are under constant bombardment from synaptic inputs. Background synaptic bombardment injected into layer 5 pyramidal cells modified the gain and sensitivity of neuronal responses to thalamocortical-like inputs [5]. Taken together, these results suggest that the thalamocortical system is in a different operating mode during states of intense synaptic activity. 1. Destexhe A, Rudolph M, Pare D (2003) The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci 4:739-751. 2. Sanchez-Vives MV, McCormick DA (2000) Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci 3:1027-1034. 3. Le Masson G, Renaud-Le Masson S, Debay D, Bal T (2002) Feedback inhibition controls spike transfer in hybrid thalamic circuits. Nature 417:854-858. 4. Prinz AA, Abbott LF, Marder E (2004) The dynamic clamp comes of age. Trends Neurosci 27:218-224. 5. Shu Y, Hasenstaub AR, Badoual M, Bal T, McCormick DA (2003) Barrage of synaptic activity control the gain and sensitivity of cortical neurons. J Neurosci 23:10388-10401.