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Loss of specificity in Basal Ganglia related movement disorders.

Bronfeld M, Bar-Gad I - Front Syst Neurosci (2011)

Bottom Line: Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events.We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG.Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control.

View Article: PubMed Central - PubMed

Affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

ABSTRACT
The basal ganglia (BG) are a group of interconnected nuclei which play a pivotal part in limbic, associative, and motor functions. This role is mirrored by the wide range of motor and behavioral abnormalities directly resulting from dysfunction of the BG. Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events. In the normal BG, this modulation is highly specific, with each neuron related only to a small subset of behavioral events depending on specific combinations of movement parameters and context. In many pathological conditions involving BG dysfunction and motor abnormalities, this neuronal specificity is lost. Loss of specificity (LOS) manifests in neuronal activity related to a larger spectrum of events and consequently a large overlap of movement-related activation patterns between different neurons. We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG. The prevalence of LOS in a many BG-related disorders suggests that neuronal specificity may represent a key feature of normal information processing in the BG system. Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control.

No MeSH data available.


Related in: MedlinePlus

Neural mechanisms underlying neuronal specificity. Schematic illustrations of intra-nucleus (A) and inter-nuclei (B) mechanisms underlying neuronal specificity. Red and blue filled circles represent excited and inhibited neurons, respectively. (A) In the striatum, inhibitory projections from GABAergic interneurons and collaterals from neighboring projection neurons (MSNs) enable selective activation of some MSNs while inhibiting others, in response to common excitatory cortical inputs (Based on: Tepper et al., 2004). (B) In the GPi, the combined effects of spatially focused inhibitory projections from the striatum, and spatially diffused excitatory projections from the subthalamic nucleus enable selective movement-related excitation/inhibition activity patterns (Based on: Mink, 1996).
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Figure 3: Neural mechanisms underlying neuronal specificity. Schematic illustrations of intra-nucleus (A) and inter-nuclei (B) mechanisms underlying neuronal specificity. Red and blue filled circles represent excited and inhibited neurons, respectively. (A) In the striatum, inhibitory projections from GABAergic interneurons and collaterals from neighboring projection neurons (MSNs) enable selective activation of some MSNs while inhibiting others, in response to common excitatory cortical inputs (Based on: Tepper et al., 2004). (B) In the GPi, the combined effects of spatially focused inhibitory projections from the striatum, and spatially diffused excitatory projections from the subthalamic nucleus enable selective movement-related excitation/inhibition activity patterns (Based on: Mink, 1996).

Mentions: Patterns of event-related neuronal activity are determined by spatial and temporal integrations of inputs to the neuron. Neurons of the BG integrate both “external” inputs from the thalamus and cortex as well as “internal” inputs from other neurons within the BG. Thus, LOS at the output stage of the BG may be attributed either to LOS of the inputs to the system (cortical or thalamic LOS), or to alterations in the internal processing of the information within the BG system. As described in Section “Neuronal Loss of Specificity,” LOS of BG neurons can be observed following local inactivation or disinhibition restricted to the BG, without a direct disturbance of the inputs to the system. This suggests that LOS may, in some cases, be primarily driven by dysfunctions of intrinsic BG information processing. In this section we present possible mechanisms of LOS generated or maintained internally by the BG system. Internal processing within the BG system leading to neuronal specificity may be performed either by “intra-nucleus” computation using inhibitory collaterals or interneurons (Figure 3A) or by “inter-nuclei” computation utilizing the integration of projections from multiple upstream nuclei (Figure 3B).


Loss of specificity in Basal Ganglia related movement disorders.

Bronfeld M, Bar-Gad I - Front Syst Neurosci (2011)

Neural mechanisms underlying neuronal specificity. Schematic illustrations of intra-nucleus (A) and inter-nuclei (B) mechanisms underlying neuronal specificity. Red and blue filled circles represent excited and inhibited neurons, respectively. (A) In the striatum, inhibitory projections from GABAergic interneurons and collaterals from neighboring projection neurons (MSNs) enable selective activation of some MSNs while inhibiting others, in response to common excitatory cortical inputs (Based on: Tepper et al., 2004). (B) In the GPi, the combined effects of spatially focused inhibitory projections from the striatum, and spatially diffused excitatory projections from the subthalamic nucleus enable selective movement-related excitation/inhibition activity patterns (Based on: Mink, 1996).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108383&req=5

Figure 3: Neural mechanisms underlying neuronal specificity. Schematic illustrations of intra-nucleus (A) and inter-nuclei (B) mechanisms underlying neuronal specificity. Red and blue filled circles represent excited and inhibited neurons, respectively. (A) In the striatum, inhibitory projections from GABAergic interneurons and collaterals from neighboring projection neurons (MSNs) enable selective activation of some MSNs while inhibiting others, in response to common excitatory cortical inputs (Based on: Tepper et al., 2004). (B) In the GPi, the combined effects of spatially focused inhibitory projections from the striatum, and spatially diffused excitatory projections from the subthalamic nucleus enable selective movement-related excitation/inhibition activity patterns (Based on: Mink, 1996).
Mentions: Patterns of event-related neuronal activity are determined by spatial and temporal integrations of inputs to the neuron. Neurons of the BG integrate both “external” inputs from the thalamus and cortex as well as “internal” inputs from other neurons within the BG. Thus, LOS at the output stage of the BG may be attributed either to LOS of the inputs to the system (cortical or thalamic LOS), or to alterations in the internal processing of the information within the BG system. As described in Section “Neuronal Loss of Specificity,” LOS of BG neurons can be observed following local inactivation or disinhibition restricted to the BG, without a direct disturbance of the inputs to the system. This suggests that LOS may, in some cases, be primarily driven by dysfunctions of intrinsic BG information processing. In this section we present possible mechanisms of LOS generated or maintained internally by the BG system. Internal processing within the BG system leading to neuronal specificity may be performed either by “intra-nucleus” computation using inhibitory collaterals or interneurons (Figure 3A) or by “inter-nuclei” computation utilizing the integration of projections from multiple upstream nuclei (Figure 3B).

Bottom Line: Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events.We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG.Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control.

View Article: PubMed Central - PubMed

Affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

ABSTRACT
The basal ganglia (BG) are a group of interconnected nuclei which play a pivotal part in limbic, associative, and motor functions. This role is mirrored by the wide range of motor and behavioral abnormalities directly resulting from dysfunction of the BG. Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events. In the normal BG, this modulation is highly specific, with each neuron related only to a small subset of behavioral events depending on specific combinations of movement parameters and context. In many pathological conditions involving BG dysfunction and motor abnormalities, this neuronal specificity is lost. Loss of specificity (LOS) manifests in neuronal activity related to a larger spectrum of events and consequently a large overlap of movement-related activation patterns between different neurons. We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG. The prevalence of LOS in a many BG-related disorders suggests that neuronal specificity may represent a key feature of normal information processing in the BG system. Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control.

No MeSH data available.


Related in: MedlinePlus