Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

Abstract

Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)-Cre and parvalbumin (PV)-Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6 -GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV-GPe neurons. In contrast, PV-GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6 -GPe and PV-GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease.

Ethanol Disinhibits Dorsolateral Striatal Medium Spiny Neurons Through Activation of A Presynaptic Delta Opioid Receptor

“…One candidate is the external segment of the globus pallidus. This structure sends GABAergic projections to both MSNs and FSIs in the dorsal striatum (Bevan et al, 1998;Mallet et al, 2012;Mastro et al, 2014) and these projections express pre-proenkephalin (Mallet et al, 2012). Given that the variability in the induction of EtOH-LTD at the FSI-MSN synapse is not explained by differences in FSI-MSN D and FSI-MSN ID pathways, and that DPDPE application consistently induces FSI-MSN synaptic depression, the heterogeneous expression of FSI-MSN EtOH-LTD may be due to the variability in the EtOH-induced release of the endogenous DOR agonist.…”

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

“…Fourthly, we did not consider heterogeneity within the GPe. Recent studies have demonstrated functional as well as structural dichotomy in the GPe [Mallet et al, 2012, Mastro et al, 2014, Abdi et al, 2015. As gap junctions between cortical interneurons typically couple cells of the same type (see above), it is possible that also pallidal gap junctions couple only within one population, or within both populations.…”

“…However, it has become apparent that GPe also densely inhibits striatum [Fujiyama et al, 2015], building the basis for a feedback loop between these two nuclei. Moreover, we modeled only one GPe population, although it is known that several types of GPe neurons, differing in both structure and function, exist [Mallet et al, 2012, Mastro et al, 2014, Abdi et al, 2015. Despite all this neglected detail and heterogeneity, we suggest that our model has biological relevance.…”

“…This is, however, also the case for other connectivities like inhibition. As, in general, little is known on basal ganglia micro-circuitries and how those circuitries shape activity, novel techniques like optogenetics might shed light into the roles of certain types of basal ganglia subnetworks, e. g., within GPe [Mastro et al, 2014].…”

“…For example, neuron models were highly simplified, consisting of only one compartment without axons or dendrites. Also different neuron types within GPe have been described [Mallet et al, 2012, Mastro et al, 2014, Abdi et al, 2015, but we used only one neural population within GPe. Notably, the distinct neural populations in GPe have different projection sites [Mallet et al, 2012].…”