Flow of Cortical Activity Underlying a Tactile Decision in Mice

“…a distributed-memory framework in which representations are maintained across interacting cortical and subcortical nodes rather than localized to any one anatomical structure (Christophel et al., 2017; Courtney, 2022; Guo et al., 2014; Slotnick, 2023, 2022; Stern and Hasselmo, 2022; Stokes, 2015).”

“If mice did not maintain a stable body weight, they received supplementary water(Guo et al., 2014a).”

“Previous studies using the former approach have consistently demonstrated that the ALM contributes to the execution of predictive motor commands 24,27,30 ; it is likely that the ALM supports at least the expression function.”

“On a larger spatial scale, anterior fl ow of activity across multiple cortical regions, from visual and parietal cortices to frontalareas, isthought to underlieperception,decisionmaking,andmovementexecution 7,11 – 13 , 44 .”

“12,14,26,35,36,37,38,39,40,41 Transparent windows utilizing C&B Metabond and other methacrylate-based compounds on intact skulls have remained transparent for up to 2 months and have been used for awake widefield functional imaging for up to 25 weeks.”

“This observation aligns with previous findings showing that BC is poorly suited for maintaining WM in unilateral tasks 32,33,45,46 .”

“For example, recordings revealed similarly selective persistent delay activity predicting movement direction in both ALM and its associated thalamic nuclei (Guo et al., 2017b), supporting theoretical models in which recurrent loops between areas with similar representations maintain persistent activity (Compte, 2000).”

“…platform addresses the need for fl exibility in design as head-fi xed tasks become increasingly complex and require sophisticated shaping protocols (Guo et al., 2014; Fiser et al., 2016; Henschke et al., 2020) and is suitable for use in both head-fi xed preparations as well as cases in which head-fi…”

“We used Neuropixels 1.0 arrays to record activity in mouse forelimb M1 and M2 while vGAT-ChR2-eYFP mice performed a self-paced naturalistic climbing task 13,14 .”

“Head restrained mice were trained in a two-alternative choice (2AC) task ( Guo et al., 2014a ; Churchland and Ditterich, 2012 ) to sample gustatory stimuli, wait during a delay period, and lick either a left or a right spout based on specific taste-direction associations.”

“Moreover, associative learning extends beyond sensory processing to include acquired salience, 48 cue predictiveness and uncertainty, 47 motor planning, 49,50 reward timing, 51,52 and other high-level abstract information.”

“Premotor neural activity, recorded during this task, shows changes during the delay period (Churchland et al., 2006b; Guo et al., 2014) and an important feature of delay period neural activity is a reduction in variability across trials; more variable activity at the beginning of the delay period…”

“The imaging window was adapted from the clear-skull techniques described in existing imaging studies 39, 78, 79 .”

“Indeed, previous research in rodents showed that M2 neurons link instructive sensory information with movement execution, even when the action is delayed after the sensory input has ended (Brody et al., 2003; Erlich et al., 2011; Guo et al., 2014; Komiyama et al., 2010; Kopec et al., 2015).”

“To test this, we exploited the optogenetic approach to activate ChR2-expressing PV interneurons, which is commonly used to inhibit brain regions in a targeted manner 28,29 .”

“The neural mechanisms of motor planning in rodents have been extensively studied in two-alternative forced choice (2AFC) and go-nogo tasks (Erlich et al., 2011; Sul et al., 2011; Guo et al., 2014; Chen et al., 2017).”

“15 26 Improvement of behavioral performance after discrimination learning Upon establishing a mixture discrimination paradigm and identifying the associated patterns of activity, we elected to investigate whether behavioral performance and GC neural activity could be modified by training mice in a…”

“Multiple brain regions are reportedly involved with the ALM in the perceptual delayed-response task, including the sensory cortex, medial motor cortex, thalamus, and cerebellum [9, 21-24].”

“Analogous paradigms have been developed to uncover the neural underpinnings of working memory 10–12 , motor planning 13,14 , contextual encoding 15,16 , reward prediction 17,18 , and other cognitive processes 19–22 .”

“As previously observed in skeletal motor regions 14,16,17 , activity in the FEF also reorganizes between planning and executing an eye movement, and this reorganization is preceded by a condition-invariant signal (Figure 1c). in the period of -600 ms to 0 ms prior to go-cue (movement preparation),…”

“Neurons in the supplemental somatosensory area have long-range projections to the anterior lateral motor area [88], and their long-range coordination is thought to mediate tactile decision making [88, 89].”

“From these analyses, we find for target stimuli a trend towards increased activation of frontal and parietal regions identified as a pre-motor licking region (anterior lateral motor cortex, ALM) (Guo et al., 2014; Li et al., 2016) and the sensorimotor tongue-jaw region (tjS1 and tjM1, or tjSM) (Mayrhofer et al., 2019)…”

“Optogenetic silencing of vS1 interferes with object location discrimination (Guo et al., 2014b) and object detection (Hong et al., 2018) tasks.”

“As optogenetic activation of interneurons has been shown to inactivate cortical network activity (Guo et al. 2014), this would allow for inhibition of mPFC during distinct task epochs (Fig.”

“Previous studies mainly focused on the role of ALM in orofacial motor control (18-20).”

“…STDP. Finally, several other factors must be addressed for paired stimulation of neuronal tuning function, such as the dendritic locations relative to the soma (Froemke et al., 2005, 2010), brain regions (Han et al., 2000; Fino et al., 2005; Safo and Regehr, 2008), and cell types (Lu et al., 2007).”

“Optogenetic activation of cortical GABAergic neurons has been widely used in circuit/systems neuroscience (15, 50).”

“…occur concurrently in multiple areas within the fronto-parietal cortices (Erlich et al., 2015; Goard et al., 2016); alternatively, it appears in a restricted anterior-lateral motor region of the rodent frontal cortex, from which it then spreads to other areas (Chen et al., 2017; Guo et al., 2014).”

“At the same time, a clearskull cap was added [45, 100, 120], as follows.”

“However, optogenetic inactivation of PPC during a whisker-dependent task concluded that PPC is not involved in performance in well trained mice (Guo et al., 2014).”

“, 2005) or conducting a task (Guo et al., 2014; Peron et al., 2015), with a relatively high temporal resolution (Grewe et al.”

“The calcium imaging data used for this paper was obtained through the Collaborative Research in Computational Neuroscience program (Peron et al., 2015; Guo et al., 2014; Peron et al., 2014).”

“Excitatory projection neurons in wS1 make monosynaptic connections to other neurons in many parts of the brain where sensory information is further processed to achieve sensory perception and sensorimotor coordination required for specific behaviors (Ferezou et al., 2007; Mao et al., 2011; Chen et al., 2013, 2015; Yam…”

“Subsequently, studies have focused on forelimb or licking motor behavior (Guo et al., 2014; Huber et al., 2012; Komiyama et al., 2010; Li et al., 2015a; Masamizu et al., 2014), presumably under the assumption that more complex tasks provide richer activity patterns from which to derive conclusions, but activity during…”