François Grenier

Role of Thalamic and Cortical Neurons in Augmenting Responses and Self-Sustained Activity: Dual Intracellular Recordings In Vivo

Progressively increasing (augmenting) responses are elicited in thalamocortical systems by repetitive stimuli at ∼10 Hz. Repeated pulse trains at this frequency lead to a form of short-term plasticity consisting of a persistent increase in depolarizing synaptic responses as well as a prolonged decrease in inhibitory responses. In this study, we have investigated the role of thalamocortical (TC) and neocortical neurons in the initiation of thalamically and cortically evoked augmenting responses. Dual intracellular recordings in anesthetized cats show that thalamically evoked augmenting responses of neocortical neurons stem from a secondary depolarization (mean onset latency of 11 msec) that develops in association with a diminution of the early EPSP. Two nonexclusive mechanisms may underlie the increased secondary depolarization during augmentation: the rebound spike bursts initiated in simultaneously recorded TC cells, which precede by ∼3 msec the onset of augmenting responses in cortical neurons; and low-threshold responses, uncovered by hyperpolarization in cortical neurons, which may follow EPSPs triggered by TC volleys. Thalamic stimulation proved to be more efficient than cortical stimulation at producing augmenting responses. Stronger augmenting responses in neocortical neurons were found in deeply located (<0.8 mm, layers V–VI) regular-spiking and fast rhythmic-bursting neurons than in superficial neurons. Although cortical augmenting responses are preceded by rebound spike bursts in TC cells, the duration of the self-sustained postaugmenting oscillatory activity in cortical neurons exceeds that observed in TC neurons. These results emphasize the role of interconnected TC and cortical neurons in the production of augmenting responses leading to short-term plasticity processes.

Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo

To investigate the relative impact of intrinsic and synaptic factors in the maintenance of the membrane potential of cat neocortical neurons in various states of the network, we performed intracellular recordings in vivo. Experiments were done in the intact cortex and in isolated neocortical slabs of anesthetized animals, and in naturally sleeping and awake cats. There are at least four different electrophysiological cell classes in the neocortex. The responses of different neuronal classes to direct depolarization result in significantly different responses in postsynaptic cells. The activity patterns observed in the intact cortex of anesthetized cats depended mostly on the type of anesthesia. The intracellular activity in small neocortical slabs was composed of silent periods, lasting for tens of seconds, during which only small depolarizing potentials (SDPs, presumed miniature synaptic potentials) were present, and relatively short-lasting (a few hundred milliseconds) active periods. Our data suggest that minis might be amplified by intrinsically-bursting neurons and that the persistent Na+ current brings neurons to firing threshold, thus triggering active periods. The active periods in neurons were composed of the summation of synaptic events and intrinsic depolarizing currents. In chronically-implanted cats, slow-wave sleep was characterized by active (depolarizing) and silent (hyperpolarizing) periods. The silent periods were absent in awake cats. We propose that both intrinsic and synaptic factors are responsible for the transition from silent to active states found in naturally sleeping cats and that synaptic depression might be responsible for the termination of active states during sleep. In view of the unexpected high firing rates of neocortical neurons during the depolarizing epochs in slow-wave sleep, we suggest that cortical neurons are implicated in short-term plasticity processes during this state, in which the brain is disconnected from the outside world, and that memory traces acquired during wakefulness may be consolidated during sleep.

Synthesis of new n-type isoindigo copolymers

Three new n-type copolymers were synthesized using the isoindigo monomer. 5-Octylthieno[3,4-c]pyrrole-4,6-dione (TPD), 5,5′-dioctyl-1,1′-4H-bithieno[3,4-c]pyrrole-4,4′,6,6′(5H,5′H)-tetrone (BTPD) and 3,6-bis(thiophen-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4-dione (DPP) were utilized as electron-withdrawing comonomers to obtain reduced or low bandgap n-type copolymers with deep HOMO and LUMO energy levels. The TPD and BTPD copolymers were synthesized using direct arylation polymerization and show bandgaps of 1.72 and 1.75 eV, respectively. Their LUMO and HOMO energy levels are also low at −4.2 and −6.0 eV, respectively. We investigated their electron mobility using thin film transistors and achieved electron mobility as high as 3.0 × 10−4 and 3.5 × 10−3 cm2 s−1 V−1 for the TPD and BTPD copolymers. The DPP copolymer was synthesized using Suzuki conditions and shows a low bandgap of 1.35 eV and a low LUMO energy level of −4.0 eV. The DPP copolymer exhibits an electron mobility of 2.7 × 10−4 cm2 s−1 V−1. All these polymers show interesting properties as potential electron acceptors in all-polymer solar cells.

Short‐ and medium‐term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse‐trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high‐intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast‐spiking (FS) neurones. The largest increase in the area of depolarization was found in regular‐spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self‐sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short‐ and medium‐term plasticity of neuronal responses.

Easy and versatile synthesis of new poly(thieno[3,4-d]thiazole)s

New alternating copolymers based on thieno[3,4-d]thiazole (TTz) derivatives were synthesized by Stille, Suzuki or direct (hetero)arylation polycondensation (DHAP) reactions using either benzodithiophene (BDT), dithienosilole (DTS), thieno[3,4-c]pyrrole-4,6-dione (TPD), diketopyrrolopyrrole-1,4-dione (DPP) or isoindigo units as comonomers. In particular, the direct hetero(arylation) polycondensation reaction has been shown to be a very interesting tool for a more efficient and economical access to new conjugated polymers. Modifications of the TTz moiety and of the polymer backbone show that it is possible to efficiently modulate the HOMO and LUMO energy levels of TTz-based copolymers. These conjugated polymers exhibit bandgaps between 1.07 and 1.82 eV with HOMO energy levels ranging from −5.06 to −5.48 eV and LUMO energy levels ranging from −3.61 to −4.02 eV.

Frequency-selective augmenting responses by short-term synaptic depression in cat neocortex

Thalamic stimulation at frequencies between 5 and 15 Hz elicits incremental or ‘augmenting’ cortical responses. Augmenting responses can also be evoked in cortical slices and isolated cortical slabs in vivo. Here we show that a realistic network model of cortical pyramidal cells and interneurones including short‐term plasticity of inhibitory and excitatory synapses replicates the main features of augmenting responses as obtained in isolated slabs in vivo. Repetitive stimulation of synaptic inputs at frequencies around 10 Hz produced postsynaptic potentials that grew in size and carried an increasing number of action potentials resulting from the depression of inhibitory synaptic currents. Frequency selectivity was obtained through the relatively weak depression of inhibitory synapses at low frequencies, and strong depression of excitatory synapses together with activation of a calcium‐activated potassium current at high frequencies. This network resonance is a consequence of short‐term synaptic plasticity in a network of neurones without intrinsic resonances. These results suggest that short‐term plasticity of cortical synapses could shape the dynamics of synchronized oscillations in the brain.