Papers by Violeta Lopez-huerta
Neural Plasticity, 2015
Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other wi... more Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other within distances of approximately 100 m. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP) between fast-spiking (FS) interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing), in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.
Brain Structure and Function, 2015
ABSTRACT Unfortunately, there is a typographical error in the original publication. The name of t... more ABSTRACT Unfortunately, there is a typographical error in the original publication. The name of the designer drug throughout the article should be (DREADD) hM4Di and not hM3Di. It is important not to assume a double error since hM3Dq is an excitatory receptor while hM4Di, which has been used is inhibitory as stated in the paper. There is no designer drug named hM3Di.
Brain Structure and Function, 2015
The striosome (or patch) was first identified with anatomical techniques as neurons organized in ... more The striosome (or patch) was first identified with anatomical techniques as neurons organized in a three-dimensional labyrinth inserted in and interdigitating the rest of neostriatum: the matrix. Striosome and matrix rapidly became known as two neuronal compartments expressing different biochemical markers, embryonic development and afferent and efferent connectivity. In spite of extensive intrinsic neuronal axonal and dendritic extensions supposed to exchange information between matrix and striosomes, evidence suggested the presence of independent areas. Here, we report that indeed these two areas do not exchange synaptic information. We used genetic expression of channel rhodopsin 2 carried by adeno-associated virus serotype 10 (AAVrh10) that only expresses in neurons of the matrix compartment. Whole-cell patch-clamp recordings of matrix neurons activated by light pulses consistently produced inhibitory postsynaptic currents (IPSCs), but the same manipulation did not evoke IPSCs in striosome neurons. The matrix contains both direct and indirect striatal output pathways. By targeting striatal matrix expression of designer receptors exclusively activated by a designer drug (DREADD) hM3di carried by AAVrh10, we were able to inhibit the matrix neuronal compartment of the dorsolateral striatum during performance of a learned single-pellet reach-to-grasp task. As expected, inhibition of matrix neurons by systemic administration of DREADD agonist clozapine-n-oxide interfered with performance of the learned task.
Neuropharmacology, 2015
N-methyl-D-aspartate receptors (NMDAR) are crucial for the function of excitatory neurotransmissi... more N-methyl-D-aspartate receptors (NMDAR) are crucial for the function of excitatory neurotransmission and are present at the synapse and on the extrasynaptic membrane. The major nucleus of the basal ganglia, striatum, receives a large glutamatergic excitatory input carrying information about movements and associated sensory stimulation for its proper function. Such bombardment of glutamate synaptic release results in a large extracellular concentration of glutamate that can overcome the neuronal and glial uptake homeostatic systems therefore allowing the stimulation of extrasynaptic glutamate receptors. Here we have studied the participation of their extrasynaptic type in cortically evoked responses or in the presence of NMDARs stimulation. We report that extrasynaptic NMDAR blocker memantine, reduced in a dose-dependent manner cortically induced NMDA excitatory currents in striatal neurons (recorded in zero-Mg(++) plus DNQX 10 μM). Moreover, memantine (2-4 μM) significantly reduced t...
Journal of Neuroscience, 2013
Inhibitory connections among striatal projection neurons (SPNs) called "feedback inhibition," hav... more Inhibitory connections among striatal projection neurons (SPNs) called "feedback inhibition," have been proposed to endow the striatal microcircuit with computational capabilities, such as motor sequence selection, filtering, and the emergence of alternating network states. These properties are disrupted in models of Parkinsonism. However, the impact of feedback inhibition in the striatal network has remained under debate. Here, we test this inhibition at the microcircuit level. We used optical and electrophysiological recordings in mice and rats to demonstrate the action of striatal feedback transmission in normal and pathological conditions. Dynamic calcium imaging with single-cell resolution revealed the synchronous activation of a pool of identified SPNs by antidromic stimulation. Using bacterial artificial chromosome-transgenic mice, we demonstrate that the activated neuron pool equally possessed cells from the direct and indirect basal ganglia pathways. This pool inhibits itself because of its own GABA release when stimuli are frequent enough, demonstrating functional and significant inhibition. Blockade of GABA A receptors doubled the number of responsive neurons to the same stimulus, revealing a second postsynaptic neuron pool whose firing was being arrested by the first pool. Stronger connections arise from indirect SPNs. Dopamine deprivation impaired striatal feedback transmission disrupting the ability of a neuronal pool to arrest the firing of another neuronal pool. We demonstrate that feedback inhibition among SPNs is strong enough to control the firing of cell ensembles in the striatal microcircuit. However, to be effective, feedback inhibition should arise from synchronized pools of SPNs whose targets are other SPNs pools.
Neurochemical Research, 2008
Medium spiny projection neurons (MSNs) are the main neuronal population in the neostriatum. MSNs ... more Medium spiny projection neurons (MSNs) are the main neuronal population in the neostriatum. MSNs are inhibitory and GABAergic. MSNs connect with other MSNs via local axon collaterals that produce lateral inhibition, which is thought to select cell assemblies for motor action. MSNs also receive inhibitory inputs from GABAergic local interneurons. This work shows, through the use of the paired pulse protocol, that somatostatin (SST) acts presynaptically to regulate GABA release from the terminals interconnecting MSNs. This SST action is reversible and not mediated through the release of dopamine. It is blocked by the SST receptor (SSTR) antagonist ciclosomatostatin (cicloSST). In contrast, SST does not regulate inhibition coming from interneurons. Because, SST is released by a class of local interneuron, it is concluded that this neuron helps to regulate the selection of motor acts.
Journal of Neurophysiology, 2012
International Journal of Neural Systems, 2015
The cell assembly (CA) hypothesis has been used as a conceptual framework to explain how groups o... more The cell assembly (CA) hypothesis has been used as a conceptual framework to explain how groups of neurons form memories. CAs are defined as neuronal pools with synchronous, recurrent and sequential activity patterns. However, neuronal interactions and synaptic properties that define CAs signatures have been difficult to examine because identities and locations of assembly members are usually unknown. In order to study synaptic properties that define CAs, we used optical and electrophysiological approaches to record activity of identified neurons in mouse cortical cultures. Population analysis and graph theory techniques allowed us to find sequential patterns that represent repetitive transitions between network states. Whole cell pair recordings of neurons participating in repeated sequences demonstrated that synchrony is exhibited by groups of neurons with strong synaptic connectivity (concomitant firing) showing short-term synaptic depression (STD), whereas alternation (sequential firing) is seen in groups of neurons with weaker synaptic connections showing short-term synaptic facilitation (STF). Decreasing synaptic weights of a network promoted the generation of sequential activity patterns, whereas increasing synaptic weights restricted state transitions. Thus in simple cortical networks of real neurons, basic signatures of CAs, the properties that underlie perception and memory in Hebb's original description, are already present.
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Papers by Violeta Lopez-huerta