Cortico-striatal spike-timing dependent plasticity after activation of subcortical pathways

Schulz Schulz

doi:10.3389/fnsyn.2010.00023

Abstract

Cortico-striatal spike-timing dependent plasticity (STDP) is modulated by dopamine in vitro. The present study investigated STDP in vivo using alternative procedures for modulating dopaminergic inputs. Postsynaptic potentials (PSP) were evoked in intracellularly recorded spiny neurons by electrical stimulation of the contralateral motor cortex. PSPs often consisted of up to three distinct components, likely representing distinct cortico-striatal pathways. After baseline recording, bicuculline (BIC) was ejected into the superior colliculus (SC) to disinhibit visual pathways to the dopamine cells and striatum. Repetitive cortical stimulation (∼60; 0.2 Hz) was then paired with postsynaptic spike discharge induced by an intracellular current pulse, with each pairing followed 250 ms later by a light flash to the contralateral eye (n = 13). Changes in PSPs, measured as the maximal slope normalized to 5-min pre, ranged from potentiation (∼120%) to depression (∼80%). The determining factor was the relative timing between PSP components and spike: PSP components coinciding or closely following the spike tended towards potentiation, whereas PSP components preceding the spike were depressed. Importantly, STDP was only seen in experiments with successful BIC-mediated disinhibition (n = 10). Cortico-striatal high-frequency stimulation (50 pulses at 100 Hz) followed 100 ms later by a light flash did not induce more robust synaptic plasticity (n = 9). However, an elevated post-light spike rate correlated with depression across plasticity protocols (R2 = 0.55, p = 0.009, n = 11 active neurons). These results confirm that the direction of cortico-striatal plasticity is determined by the timing of pre- and postsynaptic activity and that synaptic modification is dependent on the activation of additional subcortical inputs.

Highlights

The striatum, the main input nucleus of the basal ganglia, receives sensorimotor, cognitive, and motivational information from almost all cortical areas (McGeorge and Faull, 1989) and several thalamic nuclei (Erro et al, 2002)
Note that the maximum potential of the evoked Postsynaptic potentials (PSP) changed little when evoked at depolarized membrane potentials (Figure 1C); changes in the amplitude of evoked PSPs do not necessarily represent synaptic plastic changes
Individual maxima represented different components of the PSP, probably mediated by distinct pathways. This observation was of particular interest in experiments investigating spike-timing dependent plasticity (STDP)

Summary

Introduction

The striatum, the main input nucleus of the basal ganglia, receives sensorimotor, cognitive, and motivational information from almost all cortical areas (McGeorge and Faull, 1989) and several thalamic nuclei (Erro et al, 2002). Evaluative inputs from dopaminergic neurons in the substantia nigra pars compacta (Redgrave et al, 2008; Wickens et al, 2007a) and glutamatergic neurons in the thalamic intralaminar nuclei (Minamimoto et al, 2005; Schulz et al, 2009) signal the saliency of ongoing sensory events to broad areas of the striatum. The convergence of these different sets of inputs places the striatum in an ideal position for learning guided by experience. These observations indicate that dopamine is a critical ingredient for modulating cortico-striatal neurotransmission

Methods

Results

Conclusion