Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in L-Dopa-Induced Dyskinesia.

Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts. Furthermore, we determined changes in PV-immunoreactive cell density by PV immunolabeling combined with Wisteria floribunda agglutinin (WFA) labeling to detect FSI in a PV-independent manner. We also explored the differential expression of striatal activity-regulated cytoskeleton-associated protein (Arc) and c-Fos in both types of MSNs as a measure of neuronal activation. Our results confirm previous findings of major structural changes in dendritic spine density after nigrostriatal denervation, which are further modified in the dyskinetic condition. Moreover, the finding of differential modifications in perisomatic GABAergic connectivity and neuronal activation in MSNs suggests an attempt by the system to regain homeostasis after denervation and an imbalance between excitation and inhibition leading to the development of dyskinesia after exposure to L-DOPA.

In situ characterization of a rectifying electrical junction.

Electrical synapses play significant roles in neural processing in invertebrate and vertebrate nervous systems. The view of electrical synapses as plain bidirectional intercellular channels represents a partial picture because rectifying electrical synapses expand the complexity in the communication capabilities of neurons. Rectification derives, mostly, from the sensitivity of electrical junctions to the transjunctional potential (V(j)) across the coupled cells. We analyzed the characteristics of this sensitivity and their effect on neuronal signaling, studying rectifying junctions present in the leech nervous system. The NS neurons, a pair of premotor nonspiking neurons present in each midbody ganglion, are electrically coupled to virtually every excitatory motor neuron. Studied at rest, only hyperpolarizing signals can be transmitted from NS to the motoneurons, and only depolarizing signals are conducted in the opposite direction. Our results show that small changes in the NS membrane potential (V(m)) exerted an effective control of the firing frequency of the CV motoneurons (excitor of circular muscles). This effect revealed the existence of a threshold V(j) across which the electrical synapse shifts from a nonconducting to a conducting state. The junction can operate as a relatively symmetrical bidirectional bridge provided that the transmitted signals do not cross this threshold transjunctional potential.