Complex perceptual decisions, in which information must be integrated across multiple sources of evidence, are ubiquitous but are not well understood. Such decisions rely on sensory processing of each individual source of evidence, and are therefore vulnerable to bias if sensory processing resources are disproportionately allocated amongst visual inputs. To investigate this, we developed an implicit neurofeedback protocol embedded within a complex decision-making task to bias sensory processing in favour of one source of evidence over another. Human participants of both sexes ( N =30) were asked to report the average motion direction across two fields of oriented moving bars. Bars of different orientations flickered at different frequencies, thus inducing steady-state visual evoked potentials (SSVEPs). Unbeknownst to participants, neurofeedback was implemented to implicitly reward attention to a specific “trained” orientation (rather than any particular motion direction). As attentional selectivity for thi...

Entorhinal cortex (EC) neurons make monosynaptic connections onto distal apical dendrites of CA1 and CA2 pyramidal neurons (PNs) through the perforant path (PP) projection. Previous studies show that differences in dendritic properties and synaptic input density enable the PP inputs to produce a much stronger excitation of CA2 compared to CA1 PNs. Here, using mice of both sexes, we report that the difference in PP efficacy varies substantially as a function of presynaptic firing rate. Although a single PP stimulus evokes a 5-6 fold greater EPSP in CA2 compared to CA1, a brief high-frequency train of PP stimuli evokes a strongly facilitating postsynaptic response in CA1, with relatively little change in CA2. Furthermore, we demonstrate that blockade of NMDARs significantly reduces strong temporal summation in CA1, but has little impact on that in CA2. As a result of the differences in the frequency- and NMDAR-dependent temporal summation, naturalistic patterns of presynaptic activity evoke CA1 and CA2 respo...

Sox10 is a well-known factor to control oligodendrocyte (OL) differentiation and its expression is regulated by Olig2. As an important protein kinase, Akt has been implicated in diseases with white matter (WM) abnormalities. To study whether and how Akt may regulate OL development, we generated OL lineage cells-specific Akt1 / Akt2 / Akt3 triple conditional knockout ( Akt cTKO) mice. Both male and female mice were used. These mutants exhibit complete loss of mature OLs and unchanged apoptotic cell death in the central nervous system. We show that deletion of Akt three isoforms causes down-regulation of Sox10 and decreased levels of phosphorylated FoxO1 (pFoxO1) in the brain. In vitro analysis reveals that expression of FoxO1 with mutations on phosphorylation sites for Akt significantly represses the Sox10 promoter activity, suggesting that phosphorylation of FoxO1 by Akt is important for Sox10 expression. We further demonstrate that mutant FoxO1 without Akt phosphorylation epitopes is enriched in the Sox10...

Subcortical input engages in cortico-hippocampal information processing. Neurons of the hypothalamic supramammillary nucleus (SuM) innervate the dentate gyrus (DG) by co-releasing two contrasting fast neurotransmitters, glutamate and GABA and thereby support spatial navigation and contextual memory. However, the synaptic mechanisms by which SuM neurons regulate the DG activity and synaptic plasticity are not well understood. The DG comprises excitatory granule cells (GCs) as well as inhibitory interneurons (INs). Combining optogenetic, electrophysiological, and pharmacological approaches, we demonstrate that the SuM input differentially regulates the activities of different DG neurons in mice of either sex via distinct synaptic mechanisms. Although SuM activation results in synaptic excitation and inhibition in all postsynaptic cells, the ratio of these two components is variable and cell type-dependent. Specifically, dendrite-targeting INs receive predominantly synaptic excitation, whereas soma-targeting ...

To improve future decisions, people should seek information based on the value of information ( VOI ), which depends on the current evidence and the reward structure of the upcoming decision. When additional evidence is supplied, people should update VOI to adjust subsequent information seeking, but the neurocognitive mechanisms of this updating process remain unknown. We used a modified beads task to examine how the VOI is represented and updated in the human brain of both sexes. We theoretically derived, and empirically verified, a normative prediction that the VOI depends on decision evidence and is biased by reward asymmetry. Using fMRI, we found that the subjective VOI is represented in right dorsolateral prefrontal cortex (DLPFC). Critically, this VOI representation was updated when additional evidence was supplied, showing that DLPFC dynamically tracks the up-to-date VOI over time. These results provide new insights into how humans adaptively seek information in the service of decision making. SIGN...

Spontaneous action potential discharge (spAP) is both ubiquitous and functionally relevant during neural development. spAP remains a prominent feature of supraspinal networks in maturity, even during unconsciousness. Evidence suggests that spAP persists in mature spinal networks during wakefulness, and one function of spAP in this context could be maintenance of a ‘ready state’ to execute behaviors. The extent to which spAP persists in mature spinal networks during unconsciousness remains unclear, and its function(s), if any, are likewise unresolved. Here, we attempt to reconcile some of the questions and contradictions that emerge from the disintegrated picture of adult spinal spAP currently available. We recorded simultaneously from large populations of spinal interneurons in vivo in male rats, characterizing the spatial distribution of spAP in the lumbar enlargement and identifying subgroups of spontaneously active neurons. We find (1) concurrent spAP throughout the dorso-ventral extent of the gray matt...

Despite many observations of anterior cingulate cortex (ACC) activity related to cognition and affect in humans and nonhuman animals, little is known about the causal role of the ACC in psychological processes. Here, we investigate the ACC’s causal role in affective responding to threat in rhesus monkeys ( Macaca mulatta ), a species with an ACC largely homologous to humans in structure and connectivity. Male adult monkeys received bilateral ibotenate axon-sparing lesions to the ACC (sulcus and gyrus of areas 24, 32, and 25) and were tested in two classic tasks of monkey threat processing, the human intruder and object responsiveness tasks. Monkeys with ACC lesions did not significantly differ from controls in their overall mean reactivity towards threatening or novel stimuli. However, while control monkeys maintained their reactivity across test days, monkeys with ACC lesions reduced their reactivity towards stimuli as days advanced. Critically, this attenuated reactivity was found even when the stimuli p...

Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early postnatal life. Synaptic in vitro electrophysiology in male and female mice shows that postnatal Prox1 removal differentially affects the dynamics of excitatory inputs onto VIP bipolar and multipolar subtypes. RNA sequencing reveals that one of the downstream targets of Prox1 is the postsynaptic protein Elfn1, a constitutive regulator of presynaptic release probability. Further genetic, pharmacological and electrophysiological experiments demonstrate that removing Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Finally, overexpression experiments and analysis of native Elfn1 mRN...

When listening to speech, low-frequency cortical activity tracks the speech envelope. It remains controversial, however, whether such envelope-tracking neural activity reflects entrainment of neural oscillations or superposition of transient responses evoked by sound features. Recently, it is suggested that the phase of envelope-tracking activity can potentially distinguish entrained oscillations and evoked responses. Here, we analyze the phase of envelope-tracking in humans during passive listening, and observe that the phase lag between cortical activity and speech envelope tends to change linearly across frequency in the theta band (4-8 Hz), suggesting that the theta-band envelope-tracking activity can be readily modeled by evoked responses. Significance Statement During speech listening, cortical activity tracks the speech envelope, which is a critical cue for speech recognition. It is debated, however, what is the neural mechanism generating the envelope-tracking responses. Previous work has shown ...

Full-band DC recordings enable recording of slow electrical brain signals that are severely compromised during conventional AC recordings. However, full-band DC recordings may be limited by the amplifier’s dynamic input range and the loss of small amplitude high-frequency signals. Recently, Neuralynx has proposed full-band recordings with inverse filtering for signal reconstruction based on hybrid AC/DC-divider RRC filters that enable only partial suppression of DC signals. However, the quality of signal reconstruction for biological signals has not yet been assessed. Here, we propose a novel digital inverse filter based on a mathematical model describing RRC filter properties, which provides high computational accuracy and versatility. Second, we propose procedures for the evaluation of the inverse filter coefficients, adapted for each recording channel to minimize the error caused by the deviation of the real values of the RRC filter elements from their nominal values. We demonstrate that this approach e...