Biomedical subjects

Gianmaria Maccaferri

Publications and source records attributed to Gianmaria Maccaferri.

6 recordsLinked to original sources

PubMed2006

Propagation of postsynaptic currents and potentials via gap junctions in GABAergic networks of the rat hippocampus.

The integration of synaptic signalling in the mammalian hippocampus underlies higher cognitive functions such as learning and memory. We have studied the gap junction-mediated cell-to-cell and network propagation of GABA(A) receptor-mediated events in stratum lacunosum moleculare interneurons of the rat hippocampus. Propagated events were identified both in voltage- and current-clamp configurations. After blockade of ionotropic excitatory synaptic transmission, voltage-clamp recordings with chloride-loaded electrodes (predicted GABA(A) receptor reversal potential: 0 mV) at -15 mV revealed the unexpected presence of spontaneous events of opposite polarities. Inward events were larger and kinetically faster when compared to outward currents. Both types of events were blocked by gabazine, but only outward currents were significantly affected by the gap junction blocker carbenoxolone, indicating that outward events originated in electrically coupled neurons. These results were in agreement with computational modelling showing that propagated events were modulated in size and shape by their relative distance to the gap junction site. Paired recordings from electrically coupled interneurons performed with high- and low-chloride pipettes (predicted GABA(A) receptor reversal potentials: 0 mV and -80 mV, respectively) directly demonstrated that depolarizing postsynaptic events could propagate to the cell recorded with the low-chloride solution. Cell-to-cell propagation was abolished by carbenoxolone, and was not observed in uncoupled pairs. Application of 4-aminopyridine on slices resulted in spontaneous network activation of interneurons, which was driven by excitatory GABA(A) receptor-mediated input. Population activity was greatly depressed by carbenoxolone, suggesting that propagation of depolarizing synaptic GABAergic potentials may be a critical determinant of interneuronal synchronous bursting in the hippocampus.

4-Aminopyridine↗

PubMed2005

Electrical coupling between interneurons with different excitable properties in the stratum lacunosum-moleculare of the juvenile CA1 rat hippocampus.

Electrical coupling among GABAergic interneurons is believed to play an essential role in shaping synchronized brain network activity related to cognition and behavior. We have studied the rules governing the electrical coupling between hippocampal interneurons located in stratum lacunosum-moleculare of the CA1 hippocampus. The most frequently recorded interneuron subtype had short multipolar dendrites and a dense local axonal arborization, typical of neurogliaform cells. Electrical excitability in this class of interneurons was heterogeneous. Although injection of small current steps evoked late spiking, larger steps triggered different types of firing patterns. Trains of action potentials ranged from clearly adapting to highly irregular, with clustered or mostly regular spikes. Electrotonic and action potentials could be propagated to the coupled cells; the coupling coefficient for electrotonic signals was 0.035, which compared with 0.005 for action potentials. Electrical coupling was reversibly blocked by application of carbenoxolone. Multiple simultaneous recordings indicated that interneurons with similar and different firing patterns were electrically coupled. This visual impression was quantitatively confirmed by principal component analysis applied to variables related to membrane excitability. In fact, the probability of finding electrically coupled neurons in our sample was not dependent on the excitable properties of the cells tested and was approximately 0.34. The presence of diffuse electrical coupling among hippocampal interneurons of stratum lacunosum-moleculare with different excitability is a novel finding with important implications. For example, the promiscuity of electrical connections may endow inhibitory networks with a large degree of flexibility and regulate the computational power of the hippocampus during different synchronized states.

Action Potentials↗

PubMed2004

Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3 rat hippocampus.

Spontaneous synchronous bursting of the CA3 hippocampus in vitro is a widely studied model of physiological and pathological network synchronization. The role of inhibitory conductances during network bursting is not understood in detail, despite the fact that several antiepileptic drugs target GABA(A) receptors. Here, we show that the first manifestation of a burst event is a cell type-specific flurry of GABA(A) receptor-mediated inhibitory input to pyramidal cells, but not to stratum oriens horizontal interneurons. Moreover, GABA(A) receptor-mediated synaptic input is proportionally smaller in these interneurons compared with pyramidal cells. Computational models and dynamic-clamp studies using experimentally derived conductance waveforms indicate that both these factors modulate spike timing during synchronized activity. In particular, the different kinetics and the larger strength of GABAergic input to pyramidal cells defer action potential initiation and contribute to the observed delay of firing, so that the interneuronal activity leads the burst cycle. In contrast, excitatory inputs to both neuronal populations during a burst are kinetically similar, as required to maintain synchronicity. We also show that the natural pattern of activation of inhibitory and excitatory conductances during a synchronized burst cycle is different within the same neuronal population. In particular, GABA(A) receptor-mediated currents activate earlier and outlast the excitatory components driving the bursts. Thus, cell type-specific balance and timing of GABA(A) receptor-mediated input are critical to set the appropriate spike timing in pyramidal cells and interneurons and coordinate additional neurotransmitter release modulating burst strength and network frequency.

Action Potentials↗

PubMed2004

Stratum oriens horizontal interneurone diversity and hippocampal network dynamics.

In this last decade, the combination of differential interference contrast infrared video technology and patch-clamp techniques applied to slices in vitro has allowed the routine electrophysiological recording of visually identified central neurones. This has opened the way to the possibility of preselecting GABAergic interneurones of the hippocampus on the basis of some peculiar morphological characteristics. In particular, stratum oriens 'horizontal' interneurones are easily recognizable in living hippocampal slices because of their location and bipolar/bitufted appearance. Thus, this class of cells has rapidly risen as one of the most studied in the entire hippocampus. In this review, I will try to assemble the vast electrophysiological knowledge on these interneurones into a more focused picture, which is relevant for network activity in vitro and in vivo.

Animals↗

PubMed2003

Interneuron Diversity series: Hippocampal interneuron classifications--making things as simple as possible, not simpler.

The nervous system is made up of many specific types of neuron intricately intertwined to form complex networks. Identifying and defining the characteristic features of the many different neuronal types is essential for achieving a cellular understanding of complex activity from perception to cognition. So far, cortical GABAergic interneurons have represented the epitome of cellular diversity in the CNS. Despite the desperate need for effective classification criteria allowing a common language among neuroscientists, interneurons still evoke memories of Babel. Several approaches are now available to overcome the challenges and problems associated with the various classification systems used so far.

Animals↗

PubMed2002

Control of feedforward dendritic inhibition by NMDA receptor-dependent spike timing in hippocampal interneurons.

Two putative functional populations of feedforward interneurons with distinct spike-timing properties were identified in stratum radiatum of the CA1 rat hippocampus. Interneurons with fast (half width, <100 msec) EPSPs fired after short EPSP-spike latencies and with a high degree of temporal precision compared with cells with slow (half width, >100 msec) EPSPs. Spike timing in fast and slow interneurons occurred at different phases of the EPSPs of simultaneously activated pyramidal cells. In addition, firing of fast interneurons preceded action potentials in principal neurons, whereas action potentials in slow interneurons could either precede or follow firing in pyramidal cells. Temporal integration of separate inputs leading to synaptically evoked firing was more prominent in slow than fast interneurons. Functional diversity between the two putative populations was abolished by the NMDA receptor (NMDAR) antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP-5). The axon of both cell types was primarily restricted to striatum radiatum or to striatum lacunosum-moleculare in the case of slow cells, suggesting targeting of principal cell dendrites for the majority of the cells of this study. Indeed, firing of slow and fast interneurons generated similar unitary IPSCs (uIPSCs) in pyramidal neurons. uIPSCs were mediated by GABA(A) receptors and had in most cases small amplitudes and slow kinetics. Our results suggest that functionally heterogeneous interneurons encode the temporal properties of dendritic feedforward inhibition, and that NMDARs play an essential role in shaping the integrative properties of interneurons and in setting the timing of GABA release.

2-Amino-5-phosphonovalerate↗