Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching

Abstract

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for conditional discrimination performance in which a switch in reward-predictive cues occurs every three to six trials. The GABA agonists baclofen and muscimol infused into the prelimbic cortex significantly impaired performance leading rats to adopt an inappropriate turn strategy. The NMDA receptor antagonist D-AP5 infused into the dorsomedial striatum or prelimbic cortex and dorsomedial striatum contralateral disconnection impaired performance due to a rat failing to switch a response choice for an entire trial block in about two out of 13 test blocks. In an additional study, contralateral disconnection did not affect nonswitch discrimination performance. The results suggest that the prelimbic cortex and dorsomedial striatum are necessary to support cue-guided behavioral switching. The prelimbic cortex may be critical for generating alternative response patterns while the dorsomedial striatum supports the selection of an appropriate response when cue information must be used to flexibly switch response patterns.

Neurophysiology of rule switching in the corticostriatal circuit

“…This is not to suggest that mDS is solely acting as a cache for rule signals and not functioning as part of a search tree, but to suggest that when animals switch between learned rule-guided actions, signals in mDS might represent the development of appropriate cache of updated rule information. Together this strongly supports a critical role for dorsal striatum in mediating action selection in rule-based tasks and these electrophysiological data support previous lesion and pharmacological work(Ragozzino et al, 2002, Block et al, 2007, Lindgren et al, 2013, Baker and Ragozzino, 2014, Aoki et al, 2015). …”

“…A large body of work has identified a critical role for the medial dorsal striatum (mDS) in mediating flexible behavior(Ragozzino, 2002, Ragozzino et al, 2002, Stefani and Moghaddam, 2006, Ragozzino, 2007, McDonald et al, 2008, Castane et al, 2010, Baker and Ragozzino, 2014) and in reward and decision-making(Yin et al, 2005, Balleine et al, 2007, Balleine et al, 2009) while also highlighting how similar the functions of this corticostriatal circuit are between humans and rodents(Balleine and O'Doherty, 2010). Specifically, several studies have investigated shifting between rule based strategies rather than other forms of flexible behavior(Stefani and Moghaddam, 2006, Block et al, 2007, Lindgren et al, 2013, Baker and Ragozzino, 2014).…”

“…Specifically, several studies have investigated shifting between rule based strategies rather than other forms of flexible behavior(Stefani and Moghaddam, 2006, Block et al, 2007, Lindgren et al, 2013, Baker and Ragozzino, 2014). Lesions and pharmacological inactivation of mDS led to set shifting impairments, though the impairment was different than those observed with mPFC inactivations.…”

“…While mPFC function is thought to be more cognitive, medial dorsal striatum (mDS) is closely tied to the motor system, and action selection in mDS is thought to occur under the guidance of mPFC. Experimental and modelling data suggest a role for mDS in maintaining a novel response pattern after a rule shift(Cools, 2011, Collins and Frank, 2013, Baker and Ragozzino, 2014). Nevertheless, it is unknown whether neural correlates in mDS are dependent on mPFC for maintenance of rule guided behavior, or even if communication between mPFC and mDS is required for shifting between rule-based response strategies.…”

Control of behavioral flexibility by the lateral habenula

“…In a study which disconnected the mPFC and LHb using contralateral pharmacological inactivation, working memory was dramatically disrupted (Mathis et al 2016). Based on these data, behavioral flexibility tasks which rely on both the LHb and mPFC, such as proactive switching (Baker and Ragozzino 2014a; Baker et al 2016b), may also rely on an intact mPFC-LHb connection.…”