Multimodal Plasticity in Dorsal Striatum While Learning a Lateralized Navigation Task

Abstract

Growing evidence supports a critical role for the dorsal striatum in cognitive as well as motor control. Both lesions and in vivo recordings demonstrate a transition in the engaged dorsal striatal subregion, from dorsomedial to dorsolateral, as skill performance shifts from an attentive phase to a more automatic or habitual phase. What are the neural mechanisms supporting the cognitive and behavioral transitions in skill learning? To pursue this question, we used T-maze training during which rats transition from early, attentive (dorsomedial) to late habitual (dorsolateral) performance. Following early or late training, we performed the first direct comparison of bidirectional synaptic plasticity in striatal brain slices, and the first evaluation of striatal synaptic plasticity by hemisphere relative to a learned turn. Consequently, we find that long-term potentiation and long-term depression are independently modulated with learning rather than reciprocally linked as previously suggested. Our results establish that modulation of evoked synaptic plasticity with learning depends on striatal subregion, training stage, and hemisphere relative to the learned turn direction. Exclusive to the contralateral hemisphere, intrinsic excitability is enhanced in dorsomedial relative to dorsolateral medium spiny neurons early in training and population responses are dampened late in training. Neuronal reconstructions indicate dendritic remodeling after training, which may represent a novel form of pruning. In conclusion, we describe region-and hemisphere-specific changes in striatal synaptic, intrinsic, and morphological plasticity which correspond to T-maze learning stages, and which may play a role in the cognitive transition between attentive and habitual strategies.

Parallel, but Dissociable, Processing in Discrete Corticostriatal Inputs Encodes Skill Learning

“…Given that corticostriatal projections show forms of presynaptic modulation that have been implicated in skill learning (Yin et al, 2009; Park et al, 2014; Kheibek et al, 2009; Hawes et al, 2015), we next sought to assess whether the learning-related changes in presynaptic activity we observed reflect broader circuit-level changes in the engagement of the corticostriatal projections, or modulation at corticostriatal terminals specifically. To do so, we monitored upstream somatic activity of cortical neurons giving rise to associative and sensorimotor projections during skill learning.…”

“…Corticostriatal inputs are potently modulated at the level of their presynaptic terminals (Calabresi et al, 1990; Lovinger, 1991; Atwood et al, 2014; Park et al, 2014), and several of these modulatory processes have been implicated in action learning (Yin et al, 2009; Kheirbek et al, 2009; Hawes et al, 2015). Thus, we sought to probe for presynaptic modulation of corticostriatal projections in vivo during action learning.…”

“…Although many mechanisms could mediate this effect, including learning-related changes in striatal microcircuits that impinge on presynaptic corticostriatal function (Lovinger, 2010; Kupferschmidt & Lovinger, 2015; Girasole & Nelson, 2015; Logie et al, 2013; Blomeley et al, 2015), one particularly intriguing mechanism may involve training- induced presynaptic corticostriatal NMDA receptor-mediated Ca 2+ influx and plasticity. Indeed, corticostriatal inputs exhibit forms of synaptic potentiation following learning-related patterns of activity (DeCoteau et al, 2007; Tort et al, 2008) that are mediated by enhanced presynaptic Ca 2+ influx via NMDA receptors (Park et al, 2014), and are altered in ex vivo brain slices from rodents in early phases of procedural training (Hawes et al, 2015). …”

“…Glutamate release from corticostriatal terminals, known to drive activity in striatal medium-sized spiny projection neurons (Wilson, 1995), is potently modulated by various presynaptic signaling and plasticity processes (Calabresi et al, 1990; Lovinger, 1991; Atwood et al, 2014; Park et al, 2014). Ex vivo electrophysiology and gene deletion studies predict roles for inhibitory plasticity of corticostriatal terminals in skill learning (Yin et al, 2009; Kheirbek et al, 2009; Hawes et al, 2015). However, monitoring presynaptic function in discrete corticostriatal projections in vivo during learning is required to test these predictions, and advance a more anatomically and physiologically constrained view of how cortex communicates with striatum to encode action learning.…”

Glutamatergic metabolites are associated with visual plasticity in humans

“…LTP is typically induced by high-frequency electrical stimulation in animals [1, 6]. In addition, recent work indicates that LTP-like plasticity can also occur through training on motor tasks [7, 8] or with high frequency visual stimulation [9, 10]. Clapp et al developed a translational paradigm known to induce LTP-changes in the visual cortex in rodents, and applied it to humans utilizing EEG and fMRI studies to record LTP-like changes [5, 11, 12].…”