Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method

Abstract

Morita K. Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method. J Neurophysiol 112: 120 -146, 2014. First published March 5, 2014 doi:10.1152/jn.00625.2013.-The corticostriatal system is considered to be crucially involved in learning and action selection. Anatomical studies have shown that two types of corticostriatal neurons, intratelencephalic (IT) and pyramidal tract (PT) cells, preferentially project to dopamine D1 or D2 receptorexpressing striatal projection neurons, respectively. In contrast, an optogenetic study has shown that stimulation of IT axons evokes comparable responses in D1 and D2 cells and that stimulation of PT axons evokes larger responses in D1 cells. Since the optogenetic study applied brief stimulation only, however, the overall impacts of repetitive inputs remain unclear. Moreover, the apparent contradiction between the anatomical and optogenetic results remains to be resolved. I addressed these issues by using a computational approach. Specifically, I constructed a model of striatal response to cortical inputs, with parameters regarding short-term synaptic plasticity and anatomical connection strength for each connection type. Under the constraint of the optogenetic results, I then explored the parameters that best explain the previously reported paired-pulse ratio of response in D1 and D2 cells to cortical and intrastriatal stimulations, which presumably recruit different compositions of IT and PT fibers. The results indicate that 1) IT¡D1 and PT¡D2 connections are anatomically stronger than IT¡D2 and PT¡D1 connections, respectively, consistent with the previous findings, and that 2) IT¡D1 and PT¡D2 synapses entail short-term facilitation, whereas IT¡D2 and PT¡D1 synapses would basically show depression, and thereby 3) repetitive IT or PT inputs have larger overall impacts on D1 or D2 cells, respectively, supporting a recently proposed hypothesis on the roles of corticostriatal circuits in reinforcement learning. corticostriatal circuit; paired-pulse ratio; short-term synaptic plasticity; computational modeling; reinforcement learning THE CORTICOSTRIATAL SYSTEM is thought to play crucial roles in learning and action selection (Gerfen and Surmeier 2011), and its dysfunction has been suggested to cause various neuropsychiatric disorders (Shepherd 2013). There are two types of corticostriatal neurons, intratelencephalic (IT) cells and pyramidal tract (PT) cells (Cowan and Wilson 1994;Levesque et al. 1996;Parent and Parent 2006;Reiner et al. 2010), and two types of striatal projection neurons, striatonigral (direct pathway) and striatopallidal (indirect pathway) medium spiny neurons (dMSNs and iMSNs) that express dopamine D1 and D2 receptors, respectively (Gerfen and Surmeier 2011). Regarding the connections between these distinct cell populations, anatomical studies have shown that IT and PT cells preferentially target dMSNs and iMSNs, respectively (Lei et al. 2004;Reiner et ...

The functional logic of corticostriatal connections

“…The preferential distribution of contacts from IT to dSPN and PT to iSPN was first inferred from the size/frequency distribution of axospinous terminals upon the two types of SPN and supported—if with lesser bias—by direct identification of IT and PT terminals (IT terminals labelled from contralateral M1, and PT terminals labelled by tracer transported from the ipsilateral pyramidal tract) (Lei et al 2004; Reiner et al 2010; Deng et al 2015). According to a computational modelling study, the physiological mode of synaptic transmission is another variable, IT to dSPN and PT to iSPN (the preferred contacts) being facilitatory, and the reverse contacts being depressive (Morita 2014). Hence, the relative drive imparted to each class of SPN may depend critically upon the time course of activity in the two corticostriatal populations (as depressive synapses have higher baseline probability of transmitter release).…”

“…f Scarce and widespread; longer terminalsScarce and widespread; shorter terminalsStriatal terminals (e.m.) a,g,h Large (50 % wider diameter)SmallPreferential contact with striatal SPN g,h dSPN 36 %dSPN 54 %iSPN 64 %iSPN 46 %Short-term synaptic action upon dSPN i DepressiveFacilitatoryShort-term synaptic action upon iSPN i FacilitatoryDepressive

l.m. light microscope, e.m. electron microscope a Reiner et al (2003), b  Wilson (1987), c  Cowan and Wilson (1994), d  Morishima and Kawaguchi (2006), e  Kita and Kita (2012), f  Parent and Parent (2006), g  Reiner et al (2010), h  Deng et al (2015), i  Morita (2014)

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“…light microscope, e.m. electron microscope a Reiner et al (2003), b  Wilson (1987), c  Cowan and Wilson (1994), d  Morishima and Kawaguchi (2006), e  Kita and Kita (2012), f  Parent and Parent (2006), g  Reiner et al (2010), h  Deng et al (2015), i  Morita (2014)…”

Spine Enlargement of Pyramidal Tract-Type Neurons in the Motor Cortex of a Rat Model of Levodopa-Induced Dyskinesia

“…IT-type inputs to dSPNs and PT-type inputs to iSPNs may show short-term facilitation, whereas IT-type inputs to iSPNs and PT-type inputs to dSPNs may show short-term depression (Morita, 2014). IT-dSPN and PT-iSPN synapses evoke short-term facilitation, whereas IT-iSPN and PT-dSPN synapses evoke depression (Shipp, 2017).…”

Talking Convergence: Growing Evidence Links FOXP2 and Retinoic Acid in Shaping Speech-Related Motor Circuitry

“…If these hypotheses are applied to a computational model of motor sequencing (Morita et al, 2012; Morita, 2014), several possible consequences emerge. On the circuit-function level, FoxP2 and RA disruptions would impair D1R-MSNs function, and hence the “go” signal in motor control (Sippy et al, 2015, Figure 1B).…”