Dopamine-Dependent Long-Term Depression Is Expressed in Striatal Spiny Neurons of Both Direct and Indirect Pathways: Implications for Parkinson's Disease

The basal ganglia (BG) have been hypothesized to implement a reinforcement learning algorithm. However, it is not clear how information is processed along this network, thus enabling it to perform its functional role. Here we present three different encoding schemes of visual cues associated with rewarding, neutral, and aversive outcomes by BG neuronal populations.We studied the response profile and dynamical behavior of two populations of projection neurons [striatal medium spiny neurons (MSNs), and neurons in the external segment of the globus pallidus (GPe)], and one neuromodulator group [striatal tonically active neurons (TANs)] from behaving monkeys. MSNs and GPe neurons displayed sustained average activity to cue presentation. The population average response of MSNs was composed of three distinct response groups that were temporally differentiated and fired in serial episodes along the trial. In the GPe, the average sustained response was composed of two response groups that were primarily differentiated by their immediate change in firing rate direction. However, unlike MSNs, neurons in both GPe response groups displayed prolonged and temporally overlapping persistent activity. The putamen TANs stereotyped response was characterized by a single transient response group. Finally, the MSN and GPe response groups reorganized at the outcome epoch, as different task events were reflected in different response groups.Our results strengthen the functional separation between BG neuromodulators and main axis neurons. Furthermore, they reveal dynamically changing cell assemblies in the striatal network of behaving primates. Finally, they support the functional convergence of the MSN response groups onto GPe cells.

Section: Possible Different Sources Of Innervation Of Different Msn Rsupporting

confidence: 91%

Temporal Convergence of Dynamic Cell Assemblies in the Striato-Pallidal Network

Adler¹,

Katabi²,

Finkes³

et al. 2012

“…7 A, B; p Ͻ 0.01), similarly to the transgenic Th-EGFP mice. Thus, even if in some transgenic BAC-EGFP mouse lines the DAergic system has been abnormally modified (Bagetta et al, 2011;Kramer et al, 2011), the EGFP labeling or mouse background line were not responsible for the THIP-induced plasticity in this study.…”

Section: Mechanisms Of Thip-induced Glutamate Plasticitymentioning

confidence: 67%

GABA Site Agonist Gaboxadol Induces Addiction-Predicting Persistent Changes in Ventral Tegmental Area Dopamine Neurons But Is Not Rewarding in Mice or Baboons

Vashchinkina¹,

Panhelainen²,

Vekovischeva³

et al. 2012

In behavioral experiments, we found neither acute reinforcement in intravenous selfadministration sessions with THIP at relevant doses using a yoked control paradigm in mice nor in baboons using a standard paradigm for assessing drug abuse liability; nor was any place preference found after conditioning sessions with various doses of THIP but rather a persistent aversion in 6 mg/kg THIP-conditioned mice. In summary, we found that activation of extrasynaptic ␦-subunit-containing GABA A receptors leads to glutamate receptor plasticity of VTA dopamine neurons, but is not rewarding, and, instead, induces aversion.

“…Although the contribution of striatal synaptic plasticity to motor learning has been postulated (Costa et al, 2004;Pisani et al, 2005;Calabresi et al, 2007), more recent work highlights the potential contribution of experience-dependent corticostriatal plasticity to motor impairments in Parkinson's disease (PD; Kreitzer and Malenka, 2007;Shen et al, 2008;Beeler et al, 2010;. Dopamine acutely alters medium spiny neuron (MSN) excitability in the striatonigral and striatopallidal pathways (Nicola et al, 2000;Surmeier et al, 2007) and these acute effects are the basis for classic models of PD (Penney and Young, 1986;Albin et al, 1989;DeLong, 1990;Mink, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence suggests that dopamine denervation can induce an inversion in the direction of plasticity at corticostriatal synapses, particularly in the striatopallidal pathway, such that conditions that normally induce long-term depression (LTD) will instead yield long-term potentiation (LTP; Kreitzer and Malenka, 2007;Shen et al, 2008;Fino et al, 2010). Dopamine denervation or blockade results in D2-mediated aberrant learning, which is experience and task specific (Wiecki et al, 2009;Beeler et al, 2010;.…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP and Afferent Activity Govern Bidirectional Synaptic Plasticity in Striatopallidal Neurons

Augustin¹,

Beeler

McGehee

et al. 2014

Recent experimental evidence suggests that the low dopamine conditions in Parkinson's disease (PD) cause motor impairment through aberrant motor learning. Those data, along with computational models, suggest that this aberrant learning results from maladaptive corticostriatal plasticity and learned motor inhibition. Dopaminergic modulation of both corticostriatal long-term depression (LTD) and long-term potentiation (LTP) is proposed to be critical for these processes; however, the regulatory mechanisms underlying bidirectional corticostriatal plasticity are not fully understood. Previously, we demonstrated a key role for cAMP signaling in corticostriatal LTD. In this study, mouse brain slices were used to perform a parametric experiment that tested the impact of varying both intracellular cAMP levels and the strength of excitatory inputs on corticostriatal plasticity. Using slice electrophysiology in the dorsolateral striatum, we demonstrate that both LTP and LTD can be sequentially induced in the same D2-expressing neuron and that LTP was strongest with high intracellular cAMP and LFS, whereas LTD required low intracellular cAMP and high-frequency stimulation. Our results provide a molecular and cellular basis for regulating bidirectional corticostriatal synaptic plasticity and may help to identify novel therapeutic targets for blocking or reversing the aberrant synaptic plasticity that likely contributes to motor deficits in PD.