Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing.

The amygdala, hippocampus, and subgenual cortex area 25 (A25) are engaged in complex cognitive-emotional processes. Yet pathway interactions from hippocampus and A25 with postsynaptic sites in amygdala remain largely unknown. In rhesus monkeys of both sexes, we studied with neural tracers how pathways from A25 and hippocampus interface with excitatory and inhibitory microcircuits in amygdala at multiple scales.

The inevitable inequality of cortical columns.

The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensory systems. Connectional studies and molecular markers pointed to widespread presence of modular label that necessitated revision of the classical concept of columns. The general principle of cortical systematic variation in laminar structure is at the core of cortical organization.

Pathways for Contextual Memory: The Primate Hippocampal Pathway to Anterior Cingulate Cortex.

The anterior cingulate cortex (ACC) is one of the few prefrontal areas that receives robust direct hippocampal terminations. This pathway may enable current context and past experience to influence goal-directed actions and emotional regulation by prefrontal cortices. We investigated the still ill-understood organization of the pathway from anterior hippocampus to ACC (A24a, A25, A32) to identify laminar termination patterns and their postsynaptic excitatory and inhibitory targets from system to synapse in rhesus monkeys.

Specificity of Primate Amygdalar Pathways to Hippocampus.

The amygdala projects to hippocampus in pathways through which affective or social stimuli may influence learning and memory. We investigated the still unknown amygdalar termination patterns and their postsynaptic targets in hippocampus from system to synapse in rhesus monkeys of both sexes. The amygdala robustly innervated the stratum lacunosum-moleculare layer of cornu ammonis fields and uncus anteriorly.

Cortical Connections Position Primate Area 25 as a Keystone for Interoception, Emotion, and Memory.

The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emotional expression and equilibrium. A25 has a key role in affective networks, and its disruption has been linked to mood disorders, but its cortical connections have yet to be systematically or fully studied. Using neural tracers in rhesus monkeys, we found that A25 was densely connected with other ventromedial and posterior orbitofrontal areas associated with emotions and homeostasis.

How the prefrontal executive got its stripes.

Pathways from cortical and subcortical structures give the prefrontal cortex a panoramic view of the sensory environment and the internal milieu of motives and drives. The prefrontal cortex also receives privileged information from the output of the basal ganglia and cerebellum and innervates widely the inhibitory thalamic reticular nucleus that gates thalamo-cortical communication. Connections, in general, are strongly related to the systematic structural variation of the cortex that can be traced to development.

The intercalated nuclear complex of the primate amygdala.

The organization of the inhibitory intercalated cell masses (IM) of the primate amygdala is largely unknown despite their key role in emotional processes. We studied the structural, topographic, neurochemical and intrinsic connectional features of IM neurons in the rhesus monkey brain. We found that the intercalated neurons are not confined to discrete cell clusters, but form a neuronal net that is interposed between the basal nuclei and extends to the dorsally located anterior, central, and medial nuclei of the amygdala.

The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus.

In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling.

The anterior cingulate cortex may enhance inhibition of lateral prefrontal cortex via m2 cholinergic receptors at dual synaptic sites.

The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortices (DLPFC) share robust excitatory connections. However, during rapid eye movement (REM) sleep, when cortical activity is dominated by acetylcholine, the ACC is activated but DLPFC is suppressed. Using pathway tracing and electron microscopy in nonhuman primates (Macaca mulatta), we tested the hypothesis that the opposite states may reflect specific modulation by acetylcholine through strategic synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter release presynaptically, but are thought to be excitatory postsynaptically.

Anterior cingulate synapses in prefrontal areas 10 and 46 suggest differential influence in cognitive control.

Dorsolateral prefrontal areas 46 and 10 are involved in distinct aspects of cognition. Area 46 has a key role in working memory tasks, and frontopolar area 10 is recruited in complex multitask operations. Both areas are innervated by the anterior cingulate cortex (ACC), a region associated with emotions and memory but is also important for attentional control through unknown synaptic mechanisms.

Sensory pathways and emotional context for action in primate prefrontal cortex.

Connections of the primate prefrontal cortex are associated with action. Within the lateral prefrontal cortex, there are preferential targets of projections from visual, auditory, and somatosensory cortices associated with directing attention to relevant stimuli and monitoring responses for specific tasks. Return pathways from lateral prefrontal areas to sensory association cortices suggest a role in selecting relevant stimuli and suppressing distracters to accomplish specific tasks.

A randomized clinical trial investigating the relationship between aprotinin and hypercoagulability in off-pump coronary surgery.

Background: Off-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1 (PAR-1), helps propagate a thrombin burst within saphenous vein grafts. Aprotinin, used in cardiothoracic surgery mainly for its antifibrinolytic properties, also spares platelet PAR-1 activation due to thrombin. We hypothesized that this PAR-1 antagonistic property provides an antithrombotic benefit during OPCAB surgery.

Synapses with inhibitory neurons differentiate anterior cingulate from dorsolateral prefrontal pathways associated with cognitive control.

The primate dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) focus attention on relevant signals and suppress noise in cognitive tasks. However, their synaptic interactions and unique roles in cognitive control are unknown. We report that two distinct pathways to DLPFC area 9, one from the neighboring area 46 and the other from the functionally distinct ACC, similarly innervate excitatory neurons associated with selecting relevant stimuli.

Synaptic distinction of laminar-specific prefrontal-temporal pathways in primates.

Prefrontal pathways exert diverse effects in widespread cortical areas, issuing projections both to the middle layers and to layer I, which are anatomically and functionally distinct. Here we addressed the still unanswered question of whether cortical pathways that terminate in different layers are distinct at the synaptic level. We addressed this issue using as a model system the robust and functionally significant pathways from prefrontal areas 10 and 32 to superior temporal areas in rhesus monkeys.