Connectivity of the corticostriatal and thalamostriatal systems in normal and parkinsonian states: An update.

The striatum receives abundant glutamatergic afferents from the cortex and thalamus. These inputs play a major role in the functions of the striatal neurons in normal conditions, and are significantly altered in pathological states, such as Parkinson's disease. This review summarizes the current knowledge of the connectivity of the corticostriatal and thalamostriatal pathways, with emphasis on the most recent advances in the field. We also discuss novel findings regarding structural changes in cortico- and thalamostriatal connections that occur in these connections as a consequence of striatal loss of dopamine in parkinsonism.

Temporal processing in the striatum: Interplay between midbrain dopamine neurons and striatal cholinergic interneurons.

There has been considerable progress in recent years toward understanding the neuronal mechanisms mediating time perception. Notably, the striatum and its dopamine (DA) input from the ventral midbrain are considered to be central for timing on the scale of hundreds of milliseconds and seconds. The cholinergic interneurons (ChIs) of the striatum provide an extensive local innervation, which closely interacts with striatal DA afferents. Both neuronal systems have been shown to influence synaptic plasticity to shape the transfer of information through the striatum. Given their cooperative role in regulating striatal output pathways, DA and cholinergic inputs may have distinct but complementary roles in timing processes. Electrophysiological recordings from behaving animals have provided evidence that responses of midbrain DA neurons and striatal tonically active neurons (TANs), presumed ChIs, to motivationally relevant events are sensitive to the predicted time of these events; namely, changes in neuronal activity are reduced or absent at times when events are more expected, indicating that temporal aspects of prediction play an important role in the responsiveness of these two neuronal systems. Recently, new findings have further suggested that DA neurons and cholinergic TANs are both involved in the ability to keep track of the elapsed time. These two systems appear to work in parallel in initiating the timing process at the beginning of an interval to be timed. It therefore appears that DA and ChI signaling could participate in striatal processing that is crucial for the control of timing behavior.

Targeted Transgene Expression in Cholinergic Interneurons in the Monkey Striatum Using Canine Adenovirus Serotype 2 Vectors.

The striatum, the main input structure of the basal ganglia, is critical for action selection and adaptive motor control. To understand the neuronal mechanisms underlying these functions, an analysis of microcircuits that compose the striatum is necessary. Among these, cholinergic interneurons (ChIs) provide intrinsic striatal innervation whose dysfunction is implicated in neuropsychiatric diseases, such as Parkinson's disease and Tourette syndrome. The ability to experimentally manipulate the activity of ChIs is critical to gain insights into their contribution to the normal function of the striatum and the emergence of behavioral abnormalities in pathological states. In this study, we generated and tested CAV-pChAT-GFP, a replication-defective canine adenovirus type 2 (CAV-2) vector carrying the green fluorescent protein (GFP) sequence under the control of the human choline acetyltransferase (ChAT) promoter. We first tested the potential specificity of CAV-pChAT-GFP to label striatal ChIs in a rat before performing experiments on two macaque monkeys. In the vector-injected rat and monkey striatum, we found that GFP expression preferentially colocalized with ChAT-immunoreactivity throughout the striatum, including those from local circuit interneurons. CAV-2 vectors containing transgene driven by the ChAT promoter provide a powerful tool for investigating ChI contributions to circuit function and behavior in nonhuman primates.

Differences between Dorsal and Ventral Striatum in the Sensitivity of Tonically Active Neurons to Rewarding Events.

Within the striatum, cholinergic interneurons, electrophysiologically identified as tonically active neurons (TANs), represent a relatively homogeneous group in terms of their functional properties. They display typical pause in tonic firing in response to rewarding events which are of crucial importance for reinforcement learning. These responses are uniformly distributed throughout the dorsal striatum (i.e., motor and associative striatum), but it is unknown, at least in monkeys, whether differences in the modulation of TAN activity exist in the ventral striatum (i.e., limbic striatum), a region specialized for processing of motivational information. To address this issue, we examined the activity of dorsal and ventral TANs in two monkeys trained on a Pavlovian conditioning task in which a visual stimulus preceded the delivery of liquid reward by a fixed time interval. We found that the proportion of TANs responding to the stimulus predictive of reward did not vary significantly across regions (58%-80%), whereas the fraction of TANs responding to reward was higher in the limbic striatum (100%) compared to the motor (65%) and associative striatum (52%). By examining TAN modulation at the level of both the population and the individual neurons, we showed that the duration of pause responses to the stimulus and reward was longer in the ventral than in the dorsal striatal regions. Also, the magnitude of the pause was greater in ventral than dorsal striatum for the stimulus predictive of reward but not for the reward itself. We found similar region-specific differences in pause response duration to the stimulus when the timing of reward was less predictable (fixed replaced by variable time interval). Regional variations in the duration and magnitude of the pause response were transferred from the stimulus to reward when reward was delivered in the absence of any predictive stimulus. It therefore appears that ventral TANs exhibit stronger responses to rewarding stimuli, compared to dorsal TANs. The high proportion of responsive neurons, combined with particular response features, support the notion that the ventral TAN system can be driven by specific synaptic inputs arising from afferent sources distinct from those targeting the dorsal TAN system.