View that glutamatergic signaling is functionally uniform needs to change. Different classes of glutamate signaling.
Drivers and modulators: class1 and class 2 Glutamatergic Pathways. First seen in thalamus - distinction between retinal feedforward and cortical feedback. Drivers are larger initial excitatoion and show paired-pulse depression. Facilitators have smaller initial excitation and paired-pulse facilitation.
Table 1. Properties of class 1 and class 2 pathways
- Class 1/Driver (e.g., Retinal)
- Large EPSPs
- Synapses show paired-pulse depression
- Less convergence onto target
- Dense terminal arbors (type 2)
- Thick axons
- Large terminals
- Contacts target cell proximally
- Activates only iGluRs
- Class 2/Modulator (e.g., Layer 6)
- Small EPSPs
- Synapses show paired-pulse facilitation
- More convergence onto target
- Sparse terminal arbors (type 1)
- Thin axons
- Small terminals
- Contacts target cell peripherally
- Activates iGluRs and mGluRs
Fig. 1. Distinguishing driver (class 1) from modulator (class 2) inputs. A: light microscopic tracings of a driver (class 1) afferent (a retinogeniculate axon from the cat) and a modulator (class 2) afferent (a corticogeniculate axon from layer 6 of the cat). [Redrawn from Sherman and Guillery 2006.] B: modulators (red) shown contacting more peripheral dendrites than do drivers (green). Also, drivers activate only ionotropic glutamate receptors, whereas modulators also activate metabotropic glutamate receptors. C: effects of repetitive stimulation on excitatory postsynaptic potential (EPSP) amplitude: for modulators it produces paired-pulse facilitation (increasing EPSP amplitudes during the stimulus train), whereas for drivers it produces paired-pulse depression (decreasing EPSP amplitudes during the stimulus train). Also, increasing stimulus intensity for modulators (shown as different line styles) produces increasing EPSP amplitudes overall, whereas for drivers it does not; this indicates more convergence of modulator inputs compared with driver inputs.
Spikes and bursts in thalamus are caused by driving inputs from retina - (spikes in tonic mode, burst during burst mode). Cortex should interpret spikes as arising from retina.
Class 1 (drivers) and class 2 (modulators) are also seen throughout cortex. The major parameters of theses classes separate and stay clustered withing class. They stay clustered even across cortical and thalamic areas.
Class 2 can acton on metabotropic GluRs. These have longer time-scales and can also be inhibitory.
Higher-order thalamus gets its driving input from layer 5 of cortex. Class 2 input primarily comes from layer 6.
Fig. 3. Direct and transthalamic corticocortical pathways. Information relayed to cortex through thalamus is brought to thalamus via class 1 axons, most or all of which branch, with the extrathalamic branch innervating brain stem or spinal cord motor centers. This applies to inputs to both first-order (FO) and higher order (HO) thalamic relays. Thus the branches innervating thalamus (green) can be regarded as efference copies. The schematic diagram also shows the layer 6 class 2 feedback from each cortical area to thalamus, and this is contrasted with the layer 5 feed-forward corticothalamic pathways. Note that this shows cortical areas connected by 2 parallel paths: a direct one and a transthalamic one.
The class 1 inputs (both from retina and layer 5) have a common feature: they branch and project to brainstem as well as thalamus. Since thalamus is relay-like, these are efference copies. Every cortical area so far studied has a layer 5 projection to subcortical motor centers, many of which branch to thalamus.
Not much overlap in the parallel pathways - direct cortical pathways does not go subcortical, transthalamic pathway does not go to cortex.
Thalamus could be responding to unexpected motor instruction, blocking conflicting motor commands, or dynamically coupling different cortical areas. This is because of modulation by reticular nucleus and other modulatory signals.
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