Understanding how neurons of the striatum are formed and integrate into complex synaptic circuits is essential to provide insight into striatal function in health and disease. In this review, we summarize our current understanding of the development of striatal neurons and associated circuits with a focus on their embryonic origin. Specifically, we address the role of distinct types of embryonic progenitors, found in the proliferative zones of the ganglionic eminences in the ventral telencephalon, in the generation of diverse striatal interneurons and projection neurons. Indeed, recent evidence would suggest that embryonic progenitor origin dictates key characteristics of postnatal cells, including their neurochemical content, their location within striatum, and their long-range synaptic inputs. We also integrate recent observations regarding embryonic progenitors in cortical and other regions and discuss how this might inform future research on the ganglionic eminences. Last, we examine how embryonic prog...

Salvatore Incontro, Malika Sammari, Fodil Azzaz, Yanis Inglebert, Norbert Ankri, et al. (see pages [9521–9538][1]) Oriens-lacunosum-moleculare interneurons (OLMs) in hippocampal area CA1 provide feedforward inhibition at the distal dendrites of pyramidal cells and thus reduce the effects of

Ankyrin scaffolding proteins are critical for membrane domain organization and protein stabilization in many different cell types including neurons. In the cerebellum, Ankyrin-R (AnkR) is highly enriched in Purkinje neurons, granule cells, and in the cerebellar nuclei. Using male and female mice with a floxed allele for Ank1 in combination with Nestin-Cre and Pcp2-Cre mice, we found that ablation of AnkR from Purkinje neurons caused ataxia, regional and progressive neurodegeneration, and altered cerebellar output. We show that AnkR interacts with the cytoskeletal protein β3 spectrin, and the potassium channel Kv3.3. Loss of AnkR reduced somatic membrane levels of β3 spectrin and Kv3.3 in Purkinje neurons. Thus, AnkR links Kv3.3 channels to the β3 spectrin-based cytoskeleton. Our results may help explain why mutations in β3 spectrin and Kv3.3 both cause spinocerebellar ataxia. SIGNIFICANCE STATEMENT Ankyrin scaffolding proteins localize and stabilize ion channels in the membrane by linking them to the sp...

Semantic processing is an amodal process with modality-specific information integrated in supramodal ‘convergence zones’ or ‘semantic hub’ with executive mechanisms that tailor semantic representation in a task-appropriate way. One unsolved question is how frontal control region dynamically interacts with temporal representation region in semantic integration. The present study addressed this issue by using inhibitory double-pulse transcranial magnetic stimulation (TMS) over the left inferior frontal gyrus (IFG) or left posterior middle temporal gyrus (pMTG) in one of eight 40-ms time windows (TWs) (3 TWs before and 5 TWs after the identification point of speech), when human participants (12 females, 14 males) were presented with semantically congruent or incongruent gesture-speech pairs but merely identified the gender of speech. We found a TW-selective disruption of gesture-speech integration, indexed by the semantic congruency effect (i.e., a cost of reaction time due to semantic conflict), when stimula...

Little research has been done about the neural substrate of the sub-lexical level of Chinese word recognition. In particular, it is unclear how radicals participate in Chinese word processing. We compared two measures of radical combinability: position-general radical combinability (GRC) and position-specific radical combinability (SRC) depending on whether the position of the radical is taken into account. We selected characters with embedded target radicals that had different GRC and SRC measures. These measures were used as predictors in a parametric modulation analysis and a multivariate representational similarity analysis (RSA). Human participants with native Mandarin speakers (17 males and 24 females) were asked to read words in search of animal words. Results showed that SRC is a better predictor than GRC in decoding the neural patterns. Whole-brain analysis indicated that SRC is encoded bilaterally in the inferior frontal gyrus (IFG, pars opercularis and pars triangularis), the middle frontal gyru...

Children with and without dyslexia differ in their behavioural responses to visual information, particularly when required to pool dynamic signals over space and time. Importantly, multiple processes contribute to behavioural responses. Here we investigated which processing stages are affected in children with dyslexia when performing visual motion processing tasks, by combining two methods that are sensitive to the dynamic processes leading to responses. We used a diffusion model which decomposes response time and accuracy into distinct cognitive constructs, and high-density EEG. 50 children with dyslexia (24 male) and 50 typically developing children (28 male) aged 6 to 14 years judged the direction of motion as quickly and accurately as possible in two global motion tasks (motion coherence and direction integration), which varied in their requirements for noise exclusion. Following our pre-registered analyses, we fitted hierarchical Bayesian diffusion models to the data, blinded to group membership. Unb...

Much animal learning is slow, with cumulative changes in behavior driven by reward prediction errors. When the abstract structure of a problem is known, however, both animals and formal learning models can rapidly attach new items to their roles within this structure, sometimes in a single trial. Frontal cortex is likely to play a key role in this process. To examine information seeking and use in a known problem structure, we trained monkeys in an explore/exploit task, requiring the animal first to test objects for their association with reward, then, once rewarded objects were found, to re-select them on further trials for further rewards. Many cells in the frontal cortex showed an explore/exploit preference aligned with the one-shot learning in the monkeys’ behavior: the population switched from an explore state to an exploit state after a single trial of learning, but partially maintained the explore state if an error indicated that learning had failed. Binary switch from explore to exploit was not exp...

The activity-dependent expression of immediate-early genes (IEGs) has been utilised to label memory traces. However, their roles in engram specification are incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. In order to connect IEG expression at the cellular level with changes in functional-connectivity, we investigated the expression of 2 IEGs, Arc and c-Fos, in cultured hippocampal neurons. Primary neuronal cultures were treated with a chemical cocktail (4-aminopyridine, bicuculline, and forskolin) to increase neuronal activity, IEG expression, and induce chemical long-term potentiation. Neuronal firing is assayed by intracellular calcium imaging using GCaMP6m and expression of IEGs is assessed by immunofluorescence staining. We noted an emergent network property of refinement in network activity, characterized by a global downr...

In humans, age-related declines in vision, hearing, and touch coincide with changes in amplitude and latency of sensory evoked potentials. These age-related differences in neural activity may be related to a common deterioration of supra-modal brain areas (e.g., prefrontal cortex) that mediate activity in sensory cortices, or reflect specific sensorineural impairments that may differ between sensory modalities. To distinguish between these two possibilities, we measured neuroelectric brain activity while 37 young adults (18–30 years, 18 males) and 35 older adults (60–88 years, 20 males) were presented with a rapid randomized sequence of lateralized auditory, visual, and somatosensory stimuli. Within each sensory domain, we compared amplitudes and latencies of sensory-evoked responses, source activity, and functional connectivity (via phase-locking value) between groups. We found that older adults' early sensory-evoked responses were greater in amplitude than those of young adults in all three modalities, w...