RESUMO
The ventral pallidum (VP) is a central hub in the reward circuitry with diverse projections that have different behavioral roles attributed mostly to the connectivity with the downstream target. However, different VP projections may represent, as in the striatum, separate neuronal populations that differ in more than just connectivity. In this study, we performed in mice of both sexes a multimodal dissection of four major projections of the VP-to the lateral hypothalamus (VPâLH), ventral tegmental area (VPâVTA), lateral habenula (VPâLHb), and mediodorsal thalamus (VPâMDT)-with physiological, anatomical, genetic, and behavioral tools. We also tested for physiological differences between VP neurons receiving input from nucleus accumbens medium spiny neurons (MSNs) that express either the D1 (D1-MSNs) or the D2 (D2-MSNs) dopamine receptor. We show that each VP projection (1) when inhibited during a cocaine conditioned place preference (CPP) test affects performance differently, (2) receives a different pattern of inputs using rabies retrograde labeling, (3) shows differentially expressed genes using RNA sequencing, and (4) has projection-specific characteristics in excitability and synaptic input characteristics using whole-cell patch clamp. VPâLH and VPâVTA projections have different effects on CPP and show low overlap in circuit tracing experiments, as VPâVTA neurons receive more striatal input, while VPâLH neurons receive more olfactory input. Additionally, VPâVTA neurons are less excitable, while VPâLH neurons are more excitable than the average VP neuron, a difference driven mainly by D2-MSN-responding neurons. Thus, VPâVTA and VPâLH neurons may represent largely distinct populations of VP neurons.
Assuntos
Prosencéfalo Basal , Cocaína , Vias Neurais , Recompensa , Animais , Camundongos , Prosencéfalo Basal/fisiologia , Masculino , Cocaína/farmacologia , Cocaína/administração & dosagem , Feminino , Vias Neurais/fisiologia , Camundongos Endogâmicos C57BL , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Área Tegmentar Ventral/fisiologia , Área Tegmentar Ventral/citologiaRESUMO
The firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs, and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Future experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.