Biological oscillations can be controlled by a small population of rhythmic pacemaker cells, or in the brain, they also can emerge from complex cellular and circuit-level interactions. Whether and how these mechanisms are combined to give rise to oscillatory patterns that govern cognitive function are not well understood. For example, the activity of hippocampal networks is temporally coordinated by a 7- to 9-Hz local field potential (LFP) theta rhythm, yet many individual cells decouple from the LFP frequency to oscillate at frequencies ∼1 Hz higher. To better understand the network interactions that produce these complex oscillatory patterns, we asked whether the relative frequency difference between LFP and individual cells is retained when the LFP frequency is perturbed experimentally. We found that rhythmic optogenetic stimulation of medial septal GABAergic neurons controlled the hippocampal LFP frequency outside of the endogenous theta range, even during behavioral states when endogenous mechanisms would otherwise have generated 7- to 9-Hz theta oscillations. While the LFP frequency matched the optogenetically induced stimulation frequency, the oscillation frequency of individual hippocampal cells remained broadly distributed, and in a subset of cells including interneurons, it was accelerated beyond the new base LFP frequency. The inputs from septal GABAergic neurons to the hippocampus, therefore, do not appear to directly control the cellular oscillation frequency but rather engage cellular and circuit mechanisms that accelerate the rhythmicity of individual cells. Thus, theta oscillations are an example of cortical oscillations that combine inputs from a subcortical pacemaker with local computations to generate complex oscillatory patterns that support cognitive functions.

We have examined satellite glial cell (SGC) proliferation in trigeminal ganglia following chronic constriction injury of the infraorbital nerve. Using BrdU labeling combined with immunohistochemistry for SGC specific proteins we positively confirmed proliferating cells to be SGCs. Proliferation peaks at approximately 4 days after injury and dividing SGCs are preferentially located around neurons that are immunopositive for ATF-3, a marker of nerve injury. After nerve injury there is an increase GFAP expression in SGCs associated with both ATF-3 immunopositive and immunonegative neurons throughout the ganglia. SGCs also express the non-glial proteins, CD45 and CD163, which label resident macrophages and circulating leukocytes, respectively. In addition to SGCs, we found some Schwann cells, endothelial cells, resident macrophages, and circulating leukocytes were BrdU immunopositive.

The hippocampal CA2 region is essential for social memory and has been implicated in neuropsychiatric disorders. However, little is known about how CA2 neural activity encodes social interactions and how this coding is altered in disease. We recorded from CA2 pyramidal neurons as mice engaged in social interactions and found that while CA2 failed to stably represent spatial location, CA2 activity encoded contextual changes and novel social stimuli. In the Df(16)A +/mouse model of the human 22q11.2 microdeletion, a major schizophrenia risk factor, CA2 activity showed a surprising increase in spatial coding while failing to encode social novelty, consistent with the social memory deficit in these mice. Previous work has shown that CA2 pyramidal neurons are hyperpolarized in Df(16)A +/-mice, likely as a result of upregulation of TREK-1 K + current. We found that administration of a TREK-1 antagonist rescued the social memory deficits and restored normal CA2 coding properties in Df(16)A +/-mice, supporting a crucial role for CA2 in the encoding of novel social stimuli and social dysfunction..

21 22 current. We found that administration of a TREK-1 antagonist rescued the social memory deficits 35 and restored normal CA2 coding properties in Df(16)A +/-mice, supporting a crucial role for CA2 in 36 the encoding of novel social stimuli and social dysfunction. 37 38 39Recent studies indicate that the long overlooked hippocampal CA2 subregion is a critical 50 component of the circuit necessary for encoding social information into declarative memory. Both 51 short and long-term silencing of dorsal CA2 prevents social memory formation, consolidation and 52 recall 10-12 . Although dorsal CA2 provides strong input to dorsal CA1, recently our laboratory found 53 that social memory depends on the CA2 projections to ventral CA1 10 , an area that is also required 54 for social memory and that can encode social engrams 13,14 . However, at present, it is unclear as 55 to whether and how dorsal CA2 itself encodes social information that could be relevant for social 56 memory. 57Previous studies have found that CA2 spatial firing properties clearly differ from those of 58 neighboring dorsal CA1 and CA3 regions. Thus, CA2 place fields have lower spatial information 59 than those in CA1 or CA3 [15][16][17][18] . CA2 place fields are spatially unstable in the same environment 60 over time 15 , showing clear differences with the more stable and spatially precise CA1 place cell 61 firing. CA2 activity is also more sensitive to contextual change than CA1 and CA3 19 . Of interest, 62 CA2 place fields globally remap in the presence of novel objects or of familiar or novel social 63 stimuli 16 , although whether CA2 firing contains specific social information that is relevant to social 64 memory remains unkown. 65The role of CA2 in social memory is of particular clinical relevance as postmortem 66 hippocampal tissue from individuals with schizophrenia or bipolar disorder reveal a 30% decrease 67 in the number of parvalbumin positive interneurons selectively in CA2, with no changes in other 68 hippocampal regions 20,21 . A similar CA2-selective loss of PV+ interneurons is observed in the 69Df (16)A +/-mouse model of the human 22q11.2 microdeletion 22 , which confers a 30-fold increase 70 in the risk of developing schizophrenia 23 . Although the decrease in inhibition might be expected 71 to enhance CA2 pyramidal neuron (PN) activity and thus enhance social memory, these mice 72 actually have a profound deficit in social memory 22 . This behavioral deficit may reflect the fact 73 that, in addition to the decreased inhibition, CA2 PNs become hyperpolarized in these mice, likely 74 as a result of the upregulation of the TREK-1 two-pore K+ channel, which is normally highly 75 enriched in CA2 22 . It remains an open question as to whether and how the opposing actions of 76 decreased CA2 inhibition and hyperpolarization of CA2 principal cells affect their in vivo firing 77 properties. Additionally, the role of TREK-1 upregulation in the social memory deficits seen in the 78 Df(16)A +/-mice has not been explored at either the behavior...

Background One in five adults in the US experience mental illness and over half of these adults do not receive treatment. In addition to the access gap, few innovations have been reported for ensuring the right level of mental healthcare service is available at the right time for individual patients. Methods Historical observational clinical data was leveraged from a virtual healthcare system. We conceptualize mental healthcare services themselves as therapeutic interventions and develop a prototype computational framework to estimate their potential longitudinal impacts on depressive symptom severity, which is then used to assess new treatment schedules and delivered to clinicians via a dashboard. We operationally define this process as “session dosing”: 497 patients who started treatment with severe symptoms of depression between November 2020 and October 2021 were used for modeling. Subsequently, 22 mental health providers participated in a 5-week clinical quality improvement (QI) pilot, where they utilized the prototype dashboard in treatment planning with 126 patients. Results The developed framework was able to resolve patient symptom fluctuations from their treatment schedules: 77% of the modeling dataset fit criteria for using the individual fits for subsequent clinical planning where five anecdotal profile types were identified that presented different clinical opportunities. Based on initial quality thresholds for model fits, 88% of those individuals were identified as adequate for session optimization planning using the developed dashboard, while 12% supported more thorough treatment planning (e.g. different treatment modalities). In the clinical pilot, 90% of clinicians reported using the dashboard a few times or more per member. Although most clinicians (67.5%) either rarely or never used the dashboard to change session types, numerous other discussions were enabled, and opportunities for automating session recommendations were identified. Conclusions It is possible to model and identify the extent to which mental healthcare services can resolve depressive symptom severity fluctuations. Implementation of one such prototype framework in a real-world clinic represents an advancement in mental healthcare treatment planning; however, investigations to assess which clinical endpoints are impacted by this technology, and the best way to incorporate such frameworks into clinical workflows, are needed and are actively being pursued.