Striatal outputs

The basis of striatal patch-matrix organization is the segregation of striatal medium spiny neurons that have projections to different components of the substantia nigra and entopeduncular nucleus (Gerfen 1984, 1985 Gerfen et al. 1985). Neurons in the patch compartment project to the location of the ventral tier dopamine neurons, whereas neurons in the matrix compartment project to the location of GABA neurons in the 

These latter studies have demonstrated that the dendrites may take tortuous paths to remain confined within a particular compartment. In particular, patch neurons are often seen to have recurved dendrites that dutifully respect the borders between the patch and matrix compartments. This organization of the dendrites of medium spiny neurons suggests that afferents from outside the striatum that target a particular compartment 

The determination of the compartmental target of neurons in different sublaminae of the prelimbic cortex was based on a large number of cases of injections of PHA-L 

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Adenosine A2a receptors are localized to the indirect striatal output function and control motor behavior. Istradefylline is a novel adenosine A2a receptor antagonist, which demonstrated a clinically meaningful reduction in motor fluctuations in L-DOPA-treated patients with established motor complications, and is safe and well tolerated. 

B) (4) Block the action of any NT released from the neurons of striatal output path-... 

The production of DA from levodopa should restore the normal striatal picture from that proposed for PD by inhibiting striatal output pathways (Fig. 15.8). It may... 

GABA is the predominant intrinsic transmitter of the basal ganglia. Inhibition and disinhibition are considered to be the most important modes of information transfer in the basal ganglia. Ninety-five percent of all neurons in the striatum are GABAergic medium spiny neurons. These neurons are the striatal output neurons. The medium spiny neurons which give rise to the direct pathway also contain substance P or dynorphin as a co-transmitter, while those striatal output neurons that give rise to the indirect pathway contain enkephalin as a co-transmitter. Most striatal interneurons, as well as neurons in GPe, GPi and SNr are also GABAergic. Because striatal and GPe... 

Dopamine is a catecholamine (see Chapter 10 and Fig. 31.2) whose actions are mediated by dopamine receptors that are classified as Dj-like (Dj, D5) or D2-like (D2, D3, D4). Dopamine actions on Dj receptors exert an excitatory effect, whereas the actions of dopamine on D2 receptors inhibit neuronal activity. The loss of striatal dopamine produces an imbalance in information processing in the neostriatum that modifies transmission in other basal ganglia regions. Also important in neural transmission are the striatal interneurons that are found within the confines of the striatum, that use the excitatory neurotransmitter acetylcholine, and that modulate the activity of striatal output neurons. 

These neuropeptides are coexpressed with GABA in subpopulations of striatal medium-sized spiny neurons, and therefore in subsets of the fibers which target the SN. As will be mentioned further (see Section 4.3), the striatal output reaches the SN through two main circuits distinct from the anatomical and functional points of view, defined as direct and indirect pathways. Direct pathway striatal neurons express the neuropeptide substance P and dynorphin, whereas indirect pathway striatal neurons express enkephalin (see Section 6.1). 

DOPAMINE MODULATION OF STRIATAL OUTPUT THROUGH THE DIRECT AND INDIRECT PATHWAYS... 

Most of the striatal neurons containing D, mRNA, contain the peptides substance P and dynorphin on the other hand, neurons which contain preproenkephalin A do not contain D, mRNA, showing a selective association of D, receptor with the direct pathway of striatal output (Le Moine et al., 1991 Yung et al., 1995) (see Section 6.1). Although located in different striatal neuronal populations (see, Section 11.2), the D, receptor acts in concert with the D2 receptor to produce DA-mediated behaviors. 

Fig. 10 Regulation of the striatopallidal indirect GABAergic pathway A2A receptor-mediated dual excitatory modulation of the indirect pathway. Presumed action of the nondopamineigic adenosine receptor ligand in the basal ganglia circuit. Adenosine A(2A) receptors are localized to the indirect striatal output function (courtesy of Mori and Shindou, 2003)...

Considerable evidence indicates that shifts in the balance between the activity in the direct and indirect striatal output pathways and the resulting alterations in the output of the SNr and the GPi may account for the hypo- and hyperkinetic features of basal ganglia movement disorders. In summary, excessive inhibition of GPe within the indirect pathway leads to disinhibition of the STN, which in turn provides excessive excitatory drive to basal ganglia output nuclei (GPi/SNr), thus leading to excessive thalamic inhibition. This is reinforced by reduced inhibitory input to GPi/SNr through the direct pathway. Overall these effects are postulated to results in a reduction in the usual reinforcing influence of the motor circuit upon cortically initiated movements.123 (For more reviews and references see ref. 117, 124-126). 

Steiner H, Gerfen CR (1998) Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp Brain Res 123 60-76... 

Spiny projection neurons all contain glutamic acid decarboxylase (GAD) the synthetic enzyme for the neurotransmitter GABA (Kita and Kitai 1988). In addition, most of those neurons projecting to the globus pallidus alone contain the neuropeptide enkephalin, whereas most of those which project to the substantia nigra contain the neuropeptides substance P and dynorphin (Beckstead and Kersey 1985 Gerfen and Young 1988 Haber and Watson 1983). Spiny projection neurons contain different complements of neurotransmitter receptors, and other proteins that serve to characterize particular subpopulations of striatal output neurons. These will be discussed in further detail below. 

STRIATAL OUTPUT SYSTEMS TOPOGRAPHY / CONVERGENCE / DIVERGENCE... 

The topographic organization of cortical inputs to the striatum, of striatal outputs to the globus pallidus (external segment), internal segment of the globus pallidus (en-... 

There are two other distinctive features of striatal output organization. The first is the segregation of the projections of the patch-matrix compartments of the striatum. This will be discussed in a later section. The second, which has been mentioned, is the dual projection zones of striatal inputs in both the globus pallidus and substantia nigra. As will be described these dual projection systems appear also in the organization of other components of the basal ganglia, including the projection of the subthalamic nucleus. 

The functional signficance of the dual projection systems of striatal outputs may be related to the organization of the target structure of the nigral outputs. In terms of the organization of the substantia nigra projection to the superior colliculus it appears that neurons in the dorsal region project to the rostral superior colliculus, whereas those in... 

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