Cellular and synaptic properties in the lamprey striatum

The striatum is the main input structure of the basal ganglia, a group of subcortical nuclei that are central to the control of different patterns of motor behaviours and for the selection of actions, a fundamental problem facing all animals. The main focus of this thesis has been to characterize the cellular and synaptic mechanisms of the striatum and its relation to other basal ganglia nuclei in the lamprey.

To understand how the basal ganglia input structure, the striatum, processes motor related information we first needed to understand the basic architecture of the striatal microcircuitry. Individual neurons were characterized based on their electrophysiological properties and we showed that there are two main types of striatal neurons: inwardly rectifying neurons (IRNs) that are distinguished by a prominent rectification due to a Kir type K+ conductance, and non-IRNs. IRNs are in this and other respects very similar to the mammalian medium spiny projection neurons (MSNs). IRNs are projection neurons of two types, those that express substance P, dopamine receptors of D1 type and GABA, or enkephaline and D2 receptors and GABA. Non- IRNs are a mixed group of neurons and contain neurons similar to the fast-spiking type found in mammals.

We then investigated how the striatum is activated by the main excitatory inputs from the lateral pallium (the homolog of the cortex) and from thalamus. As recently demonstrated in mammals, the pallium and thalamus in lamprey provide synaptic inputs with very different dynamic properties to the striatum, as evoked by extracellular stimulation of the respective pathway. Repetitive activation of the synapses from the lateral pallium result in a progressive facilitation over several hundred milliseconds due to a low presynaptic release probability. In contrast, activation of thalamic afferents instead evokes strongly depressing synapses throughout a stimulus train due to a high presynaptic release probability. The conserved difference between the thalamic and pallial inputs most likely has functional implications for processing within striatum.

The lamprey striatum receives prominent dopaminergic innervation that, when depleted, leads to hypokinetic symptoms. As dopamine is thought to bias the striatal networks towards selecting actions by differentially modulating the excitability of D1 and D2 receptor expressing striatal projection neurons, we investigated this in lamprey. We cloned the lamprey D2 receptor and demonstrated that it was expressed in striatum. We showed that the neurons that project directly to the basal ganglia output nuclei (the substantia nigra pars reticulata (SNr) and the globus pallidus interna (GPi)) express dopamine D1 receptors, while separate populations that project to the mixed GPi/GPe nucleus express either dopamine D1 or D2 receptors. As in mammals, activation of D1 receptors furthermore leads to an increase in the excitability, whereas D2 activation decreases the excitability of IRNs.

Lastly, we identified the SNr and pedunculopontine nucleus (PPN) in lamprey and showed that the SNr provides tonic inhibition to downstream motor centers while the cholinergic neurons of the PPN modulates basal ganglia nuclei. In summary, the organization of striatum and the properties of the synaptic input, cellular properties and molecular markers are conserved throughout vertebrate evolution.

List of scientific papers

I. Ericsson J, Robertson B, Wikström MA (2007) A lamprey striatal brain slice preparation for patch-clamp recordings. J Neurosci Methods. 165:251-256.
https://doi.org/10.1016/j.jneumeth.2007.05.034

II. Ericsson J, Silberberg G, Robertson B, Wikström MA, Grillner S (2011). Striatal cellular properties conserved from lampreys to mammals. J Physiol. 589:2979-2992.
https://doi.org/10.1113/jphysiol.2011.209643

III. Ericsson J, Stephenson-Jones M, Kardamakis A, Robertson B, Silberberg G, Grillner S (2012) Evolutionarily conserved differences in pallial and thalamic short-term synaptic plasticity in striatum. [Submitted]

IV. Robertson B, Huerta-Ocampo I, Ericsson J, Stephenson-Jones M, Perez-Fernandez J, Bolam JP, Diaz-Heijtz R, Grillner S (2012). The dopamine D2 receptor gene in lamprey, its expression in the striatum and cellular effects of D2 receptor activation. PloS one. 7:e35642.
https://doi.org/10.1371/journal.pone.0035642

V. Ericsson J*, Stephenson-Jones M*, Pérez-Fernández J, Robertson B, Silberberg G, Grillner S (2012) Dopamine differentially modulates the excitability of striatal neurons in the direct and indirect pathways in lamprey. [Manuscript]

VI. Stephenson-Jones M, Ericsson J, Robertson B, Grillner S (2012) Evolution of the basal ganglia: dual output pathways conserved throughout vertebrate phylogeny. J Comp Neurol. 520(13):2957-73.
https://doi.org/10.1002/cne.23087