In the rodent whisker system, active sensing and sensorimotor integration are mediated in part by the dynamic interactions between the motor cortex (M1) and somatosensory cortex (S1). However, understanding these dynamic interactions requires knowledge about the synapses and how specific neurons respond to their input. Here, we combined optogenetics, retrograde labeling, and electrophysiology to characterize the synaptic connections between M1 and layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons in S1 of mice (both sexes). We found that M1 synapses onto IT cells displayed modest short-term depression, whereas synapses onto PT neurons showed robust short-term facilitation. Despite M1 inputs to IT cells depressing, their slower kinetics resulted in summation and a response that increased during short trains. In contrast, summation was minimal in PT neurons due to the fast time course of their M1 responses. The functional consequences of this reduced summation, however, were outweighed by...

Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crab Cancer borealis to investigate mechanisms of inter-network coordination, due to its small, well characterized feeding-related networks (gastric mill [chewing, ∼0.1 Hz]; pyloric [filtering food, ∼1 Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric- plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG...

Clinical studies of major depression (MD) generally focus on group effects, yet inter-individual differences in brain function are increasingly recognised as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2 and 8 weeks during which patients received pharmacotherapy (escitalopram, N=68), and controls (N=39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs non-responders, female vs male participants), recording sessions and individuals. Individual differences and common connectivity across groups, sessions and ...

Formation and retrieval of remote contextual memory depends on cortical engram neurons that are defined during learning. Manipulation of astrocytic Gq and Gi associated G-protein coupled receptor (GPCR) signaling has been shown to affect memory processing, but little is known about the role of cortical astrocytic Gs-GPCR signaling in remote memory acquisition and the functioning of cortical engram neurons. We assessed this by chemogenetic manipulation of astrocytes in the medial prefrontal cortex (mPFC) of male mice, during either encoding or consolidation of a contextual fear memory, while simultaneously labeling cortical engram neurons. We found that stimulation of astrocytic Gs signaling during memory encoding and consolidation did not alter remote memory expression. In line with this, the size of the mPFC engram population and the recall-induced reactivation of these neurons was unaffected. Hence, our data indicate that activation of Gs-GPCR signaling in cortical astrocytes is not sufficient to alter m...

Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing, often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crab Cancer borealis to investigate mechanisms of internetwork coordination, due to its small, well-characterized feeding-related networks (gastric mill [chewing, ∼0.1 Hz]; pyloric [filtering food, ∼1 Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric-plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG ...

The retrosplenial cortex (RSC) is a hub of diverse afferent and efferent projections thought to be involved in associative learning. RSC shows early pathology in mild cognitive impairment and Alzheimer's disease (AD), which impairs associative learning. To understand and develop therapies for diseases such as AD, animal models are essential. Given the importance of human RSC in object-location associative learning and the success of object-location associative paradigms in human studies and in the clinic, it would be of considerable value to establish a translational model of object-location learning for the rodent. For this reason, we sought to test the role of RSC in object-location learning in male rats using the object-location paired-associates learning (PAL) touchscreen task. First, increased cFos immunoreactivity was observed in granular RSC following PAL training when compared with extended pretraining controls. Following this, RSC lesions following PAL acquisition were used to explore the necessit...

Sleep's contribution to affective regulation is insufficiently understood. Previous human research has focused on memorizing or rating affective pictures and less on physiological affective responsivity. This may result in overlapping definitions of affective and declarative memories and inconsistent deductions for how rapid eye movement sleep (REMS) and slow-wave sleep (SWS) are involved. Literature associates REMS theta (4–8 Hz) activity with emotional memory processing, but its contribution to social stress habituation is unknown. Applying selective sleep stage suppression and oscillatory analyses, we investigated how sleep modulated affective adaptation toward social stress and retention of neutral declarative memories. Native Finnish participants ( N  = 29; age, M  = 25.8 years) were allocated to REMS or SWS suppression conditions. We measured physiological (skin conductance response, SCR) and subjective stress response and declarative memory retrieval thrice: before laboratory night, the next morning...

Studies on genetic robustness recently revealed transcriptional adaptation (TA) as a mechanism by which an organism can compensate for genetic mutations through activation of homologous genes. Here, we discovered that genetic mutations, introducing a premature termination codon (PTC) in the amyloid precursor protein-b ( appb ) gene, activated TA of two other app family members, appa and amyloid precursor-like protein-2 ( aplp2 ), in zebrafish. The observed transcriptional response of appa and aplp2 required degradation of mutant mRNA and did not depend on Appb protein level. Furthermore, TA between amyloid precursor protein (APP) family members was observed in human neuronal progenitor cells; however, compensation was only present during early neuronal differentiation and could not be detected in a more differentiated neuronal stage or adult zebrafish brain. Using knockdown and chemical inhibition, we showed that nonsense-mediated mRNA decay (NMD) is involved in degradation of mutant mRNA and that Upf1 and...

The paralaminar nucleus of the amygdala (PL) comprises neurons that exhibit delayed maturation. PL neurons are born during gestation but mature during adolescent ages, differentiating into excitatory neurons. These late-maturing PL neurons contribute to the increase in size and cell number of the amygdala between birth and adulthood. However, the function of the PL upon maturation is unknown, as the region has only recently begun to be characterized in detail. In this study, we investigated key defining features of the adult mouse PL; the intrinsic morpho-electric properties of its neurons, and its input and output circuit connectivity. We identify two subtypes of excitatory neurons in the PL based on unsupervised clustering of electrophysiological properties. These subtypes are defined by differential action potential firing properties and dendritic architecture, suggesting divergent functional roles. We further uncover major axonal inputs to the adult PL from the main olfactory network and basolateral am...

Animals use a combination of eye movements to track moving objects. These different eye movements need to be coordinated for successful tracking, requiring interactions between the systems involved. Here, we study the interaction between the saccadic and smooth pursuit eye movement systems in marmosets. Using a single-target pursuit task, we show that saccades cause an enhancement in pursuit following a saccade. Using a two-target pursuit task, we show that this enhancement in pursuit is selective toward the motion of the target selected by the saccade, irrespective of any biases in pursuit prior to the saccade. These experiments highlight the similarities in the functioning of saccadic and smooth pursuit eye movement systems across primates.