Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

Burkhardt, John M.

doi:10.3389/neuro.07.028.2009

Cited by 42 publications

(46 citation statements)

References 61 publications

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“…Furthermore, dopamine (DA) supplementation in Parkinson disease conditions not only abolished pathological 15-to 30-Hz β-oscillation, but also increased γ-oscillation at greater than 70 Hz (34), in association with prokinetic effects. In addition, a pharmacological blockade of DA receptors resulted in a shift from 80 to 100 Hz to 50 Hz synchrony in awake mice (35), whereas injections of psychostimulants or DA agonists in normal rats produced an opposite effect of enhancement of γ-synchrony (14), as in our R6/1 mice. Taken together, these data suggest increased DA transmission in R6/1 mice, as in HD (36), whereas a decreased nigrostratal activity and DA transmission have been reported in the R6/1 mice (37,38).…”

Section: Discussionmentioning

confidence: 95%

Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease

Cayzac

Delcasso

Paz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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In hereditary neurodegenerative Huntington disease (HD), early cognitive impairments before motor deficits have been hypothesized to result from dysfunction in the striatum and cortex before degeneration. To test this hypothesis, we examined the firing properties of single cells and local field activity in the striatum and cortex of pre-motor-symptomatic R6/1 transgenic mice while they were engaged in a procedural learning task, the performance on which typically depends on the integrity of striatum and basal ganglia. Here, we report that a dramatically diminished recruitment of the vulnerable striatal projection cells, but not local interneurons, of R6/1 mice in coding for the task, compared with WT littermates, is associated with severe deficits in procedural learning. In addition, both the striatum and cortex in these mice showed a unique oscillation at high γ-frequency. These data provide crucial information on the in vivo cellular processes in the corticostriatal pathway through which the HD mutation exerts its effects on cognitive abilities in early HD.single unit | local field potential | high γ-oscillation | operant learning | pre-motor-symptomatic R6/1 mice H untington disease (HD) is a progressive and inherited neurodegenerative disorder associated with selective degeneration of medium-sized spiny projection neurons in the striatum (1). Although the disease is well characterized by symptoms such as involuntary choreiform movements, dystonias, and rigidity, these motor symptoms have been found to be preceded by personality, mood, and cognitive disturbances (2). Some postmortem studies have also shown only limited signs of pathologic processes or cell loss in the brain despite substantial clinical evidence of HD (3), suggesting that neuronal-and, more precisely, synapticdysfunction, rather than cell death, may predominantly underlie early behavioral manifestations of the HD mutation.Studies of the effects of the mutant HD gene in several transgenic mouse models, including the R6 lines, have indeed shown changes in the membrane properties, biochemistry, and morphology of fragile striatal cells (4, 5), suggesting compromised functional integrity. They have also shown early and progressive alterations in synaptic plasticity in the corticostriatal pathway (6). These changes have been hypothesized to underlie early cognitive and behavioral deficits in transgenic mice (and patients with HD) by altering striatal information processing and transfer within basal ganglia loops.To verify this hypothesis, we recorded single-unit activity and local field potentials (LFPs) in the dorsal striatum and cortex, whereas behaviorally naive pre-motor-symptomatic R6/1 mice (7) (14-18 wk old) and age-matched WT littermates acquired an association between a nose-poke (NP) action and reward through operant learning. This procedural learning of an action-reward association is known to critically involve the striatum, a crucial site for the integration of the sensorimotor, limbic, and cognitive information required for the selecti...

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Section: Discussionmentioning

confidence: 95%

Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease

Cayzac

Delcasso

Paz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The average firing rate of medium spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs) was increased by the dopamine depletion † as Only sessions with simultaneous recordings in both sides were used. *P < 0.05. previously seen (18,19). To address the effect of dopamine depletion on the spike-LFP relationships in the dorsolateral striatum, we analyzed the phase coupling of spikes to LFP oscillations, measured during the maze runs in overtraining sessions-the time during which we found strongest effects of dopamine depletion on LFP power.…”

Section: Effects Of Dopamine Depletion On Lfp Oscillations Emerge Aftermentioning

confidence: 99%

“…Clinical evidence suggests that successful therapies for Parkinson disease reduce these abnormal LFP oscillations (3)(4)(5)(6), establishing them as a central feature of Parkinson disease. In particular, abnormally strong beta-range oscillations (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and weakened high-frequency gamma oscillations (>70 Hz) have been found in basal ganglia structures. The "antimovement" beta-band oscillations are reduced by both L-DOPA therapy and by deep brain stimulation (DBS) (3)(4)(5)(6).…”

mentioning

confidence: 99%

Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l -DOPA

Lemaire

Hernández

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by L-DOPA therapy. Under normal circumstances, oscillatory activity in these circuits is modulated as behaviors are learned and performed, but how dopamine depletion affects such modulation is not yet known. We here induced unilateral dopamine depletion in the sensorimotor striatum of rats and then recorded local field potential (LFP) activity in the dopamine-depleted region and its contralateral correspondent as we trained the rats on a conditional T-maze task. Unexpectedly, the dopamine depletion had little effect on oscillations recorded in the pretask baseline period. Instead, the depletion amplified oscillations across delta (∼3 Hz), theta (∼8 Hz), beta (∼13 Hz), and low-gamma (∼48 Hz) ranges selectively during task performance times when each frequency band was most strongly modulated, and only after extensive training had occurred. High-gamma activity (65-100 Hz), in contrast, was weakened independent of task time or learning stage. The depletion also increased spike-field coupling of fast-spiking interneurons to low-gamma oscillations. L-DOPA therapy normalized all of these effects except those at low gamma. Our findings suggest that the task-related and learning-related dynamics of LFP oscillations are the primary targets of dopamine depletion, resulting in overexpression of behaviorally relevant oscillations. L-DOPA normalizes these dynamics except at low-gamma, linked by spike-field coupling to fast-spiking interneurons, now known to undergo structural changes after dopamine depletion and to lack normalization of spike activity following L-DOPA therapy. L oss of the dopamine-containing innervation of the basal ganglia is a primary pathology in Parkinson disease, resulting, in addition to its behavioral effects, in abnormal local field potential (LFP) oscillations within cortico-basal ganglia circuits (1-4). Clinical evidence suggests that successful therapies for Parkinson disease reduce these abnormal LFP oscillations (3-6), establishing them as a central feature of Parkinson disease. In particular, abnormally strong beta-range oscillations (12-30 Hz) and weakened high-frequency gamma oscillations (>70 Hz) have been found in basal ganglia structures. The "antimovement" beta-band oscillations are reduced by both L-DOPA therapy and by deep brain stimulation (DBS) (3-6). How these observations relate to the proposed network functions of oscillatory neural activity is not yet clear. LFP oscillations have been linked not only to motor control but also to sensory perception, attention, learning, memory formation, and interregional communication (7-11). In Parkinson disease models, abnormal patterns of synchrony have been found in rest and locomotion (12)(13)(14), but the effect of dopamine loss on LFP oscillations during complex tasks requiring learning and decision making has not been explored.Here we report that dopamine depletion in the sensorimotor striatum...

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“…More specifically, a loss of FSI-mediated control of MSN spike timing in pathophysiological states can result in impaired locomotion. In dopamine-depleted states, local field potential (LFP) recordings show a decreased power of gamma oscillation and an increased power of low-frequency oscillation in the dorsal striatum (Costa et al 2006;Burkhardt et al 2009). Given that dopamine increases FSI activity by depolarization (Bracci et al 2002), such depletion could restrain FSIs from transition to up states where the power of high frequencies is enhanced (Schulz et al 2011).…”

Section: The Modulation Of Excitatory and Inhibitory Balance In Locommentioning

confidence: 99%

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Kim

Bakes

et al. 2012

Learn. Mem.

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The dorsal striatum, with its functional microcircuits galore, serves as the primary gateway of the basal ganglia and is known to play a key role in implicit learning. Initially, excitatory inputs from the cortex and thalamus arrive on the direct and indirect pathways, where the precise flow of information is then regulated by local GABAergic interneurons. The balance of excitatory and inhibitory transmission in the dorsal striatum is modulated by neuromodulators such as dopamine and acetylcholine. Under pathophysiological states in the dorsal striatum, an alteration in excitatory and inhibitory transmission may underlie dysfunctional motor control. Here, we review the cellular connections and modulation of striatal microcircuits and propose that modulating the excitatory and inhibitory balance in synaptic transmission of the dorsal striatum is important for regulating locomotion.The dorsal striatum is best known for its role in decision-making, especially in action selection and initiation through the convergence of sensorimotor, cognitive, and motivational information (DeLong 1990;Smith et al. 1998;Balleine et al. 2007). As the primary input of the basal ganglia, the striatum receives glutamatergic inputs from the cortex and thalamus and in turn projects GABAergic outputs to the globus pallidus and substantia nigra pars reticulata (SNr). Inputs from the cortex and thalamus both form excitatory synaptic connections on medium spiny neurons (MSN) in which cortical afferents are from the sensory, motor, and associational cortex (Bolam et al. 2000), and thalamic afferents are from the intralaminar thalamic nuclei (Doig et al. 2010). These glutamatergic inputs are then processed in the dorsal striatum where numerous connections between various types of neurons exist. Thus, the complexity of neuronal circuits has made it difficult to elucidate the functional roles of the striatum. Recently, studies focused on interneurons that reside in the dorsal striatum have characterized the physiological features and functional connections. For example, parvalbumin-expressing fastspiking interneurons (PV-FSI) and neuropeptide-Y positive lowthreshold spiking interneurons (NPY-LTS) form synaptic connections with MSNs and regulate the firing activity of the principal neuron MSNs (Koos and Tepper 1999;Gittis et al. 2010;Chuhma et al. 2011). These interneurons were shown to have distinct firing patterns and connections, and thus they may exert different effects on MSNs. Other crucial connections are the cholinergic, dopaminergic, and serotonergic axons that strongly innervate the dorsal striatum. These projections are essential for modulating striatal circuits and disruption of such signaling can result in movement impairments and neurological disorders such as Huntington's disease (Lovinger 2010). This review summarizes recent reports of the microcircuits present in the dorsal striatum, although serotonergic signaling is excluded, and suggests a putative role for striatal microcircuits in motor dysfunction and/or hyperactivity that ...

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Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

Cited by 42 publications

References 61 publications

Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease

Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease

Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l -DOPA

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

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