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Functional connectivity is a neurobiological notion, informally stating that there would be a strong dependence between neurons and that this dependence might be useful in understanding the way the brain encodes stimuli, programs actions, etc. However, in practice such strong dependencies are often reconstructed via Hawkes processes based on an amazingly small number of neurons, because of the very scarce observation of this very complex and huge network. We derive new simple equations, which explain how the ideal Hawkes reconstruction is linked to the covariance between the observed neurons. These equations help us in particular to understand what the Hawkes reconstruction does in two settings, synchronization and classical point process asymptotics. Moreover they might help us to also understand what is qualitatively happening at the scale of the huge unobserved network, paving the path for a possible mathematical definition of functional connectivity.

Background: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. Objective: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. Methods: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. Results: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. Conclusion: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely—compared to depression—to be associated with conversion to dementia. [ABSTRACT FROM AUTHOR]

The habenulo-interpeduncular system (HIPS) is now recognized as a critical circuit modulating aversion, reward, and social behavior. There is evidence that dysfunction of this circuit leads to psychiatric disorders. Because psychiatric diseases may originate in developmental abnormalities, it is crucial to investigate the developmental mechanisms controlling the formation of the HIPS. Thus far, this issue has been the focus of limited studies. Here, we explored the developmental processes underlying the formation of the medial habenula (MHb) and its unique output, the interpeduncular nucleus (IPN), in mice independently of their gender. We report that the Otx2 homeobox gene is essential for the proper development of both structures. We show that MHb and IPN neurons require Otx2 at different developmental stages and, in both cases, Otx2 deletion leads to disruption of HIPS subcircuits. Finally, we show that Otx2 + neurons tend to be preferentially interconnected. This study reveals that synaptically connected components of the HIPS, despite radically different developmental strategies, share high sensitivity to Otx2 expression. [ABSTRACT FROM AUTHOR]

The rat dorsomedial (DMS) and dorsolateral striatum (DLS), equivalent to caudate nucleus and putamen in primates, are required for goal-directed and habit behaviour, respectively. However, it is still unclear whether and how this functional dichotomy emerges in the course of learning. In this study we investigated this issue by recording DMS and DLS single neuron activity in rats performing a continuous spatial alternation task, from the acquisition to optimized performance. We first applied a classical analytical approach to identify task-related activity based on the modifications of single neuron firing rate in relation to specific task events or maze trajectories. We then used an innovative approach based on Hawkes process to reconstruct a directed connectivity graph of simultaneously recorded neurons, that was used to decode animal behavior. This approach enabled us to better unravel the role of DMS and DLS neural networks across learning stages. We showed that DMS and DLS display different task-related activity throughout learning stages, and the proportion of coding neurons over time decreases in the DMS and increases in the DLS. Despite theses major differences, the decoding power of both networks increases during learning. These results suggest that DMS and DLS neural networks gradually reorganize in different ways in order to progressively increase their control over the behavioral performance. Significance statement Our study helps understanding the role of the dorsomedial (DMS) and dorsolateral striatum (DLS) during the acquisition and optimization of a behavioral strategy. It is generally believed that the DMS mediates action-outcome associations, whereas the DLS supports habit behavior, but it is still unclear how these processes emerges during learning. To analyze the dynamic changes of DMS and DLS network activity across learning stages, we used a mathematical analysis combining single neuron firing rate and connectivity between neurons to decode rat behavior in a goal-directed spatial task. We demonstrated that both DMS and DLS activity supports behavioral performance throughout all learning stages, thus challenging the hypothesis of a gradual shift from DMS to DLS activity., (Copyright © 2024 Villet et al.)

Several recent reports based on microdialysis have shown that repeated injections of IFN-alpha induce reduced dopamine (DA) activity in the rodent brain, and specifically within the striatum. This mesolimbic DA system is thought to play a central role in controlling latent inhibition (LI), which refers to the phenomenon in which conditioning proceeds more slowly to an irrelevant pre-exposed (PE) stimulus. The purpose of the present experiment was to evaluate whether chronic treatment with IFN-alpha may induce similar effects on LI as other DA-depleting manipulations. Rats were injected daily, for 24 days either with 10(4)IU IFN-alpha or vehicle, while monitoring their locomotor activity in photocell cages. No changes in locomotor activity, either during the acute period after the first injection, or progressively over the chronic period were observed. LI was then evaluated in these rats with a Conditioned Taste Aversion (CTA) paradigm. Half of each group of rats were pre-exposed to the 5% sucrose Conditioned Stimulus (CS) for 30 min on three successive days before the conditioning session in which the 30 min access to the 5% sucrose solution was followed by a 0.15M injection of 127 mg/kg LiCl. Two test sessions, in which rats were given a choice between the 5% sucrose solution and water, were given 48 and 72 h after the conditioning session. The results showed moderate LI in the control group, which was considerably potentiated in the IFN-alpha group despite the absence of any change in locomotor activity. These results are interpreted as providing indirect support for the theory that suggests that LI depends on DA activity in the nucleus accumbens (NAcc).

Interferon-alpha(IFN-alpha) is used clinically in the treatment of several pathologies such as hepatitis C and various cancers. The positive therapeutic potential is however often limited by negative secondary effects which include major depression, one of the cardinal symptoms of which is anhedonia which has been operationalized as a decreased sensitivity to rewards (inability to experience pleasure). Previous studies have demonstrated the existence of anhedonia in rats following an acute injection of IFN-alpha at doses corresponding to those used in clinical applications. If this previously demonstrated anhedonia is indeed part of a depression syndrome in rats, this behavioural symptom should be reversible by the administration of antidepressants. The objective of the present experiment was to determine whether two commonly used antidepressants (desipramine and fluoxetine) were effective in ameliorating IFN-alpha-induced anhedonia in rats. The experiment consisted of two phases. In the first, the effects of daily systemic injections of 104 units/kg of IFN-alpha (or vehicle) were evaluated with the three-bottle (1%, 8%, and 32%) sucrose-consumption test. In the second phase of the experiment, in addition to continued injections of IFN-, different groups received daily injections of desipramine (7.5 mg/kg ip), fluoxetine (7.5 mg/kg ip), or vehicle. The IFN-alpha injections during Phase 1 resulted in clear anhedonia, as expressed by increased consumption of the 32% solution and decreased consumption of 1% over the 33 days of this phase. After 15 days of antidepressant treatments, 32% sucrose consumption returned to baseline values. We have therefore confirmed that IFN-alpha-induced anhedonia is susceptible to reversal following chronic antidepressant treatment and thus it may appear timely to consider the prophylactic use of such in particular patients prescribed IFN in the clinic.