title: Thalamic and Entorhinal Network Activity Differently Modulates the Functional Development of Prefrontal-Hippocampal Interactions.
abstract: Precise information flow during mnemonic and executive tasks requires the coactivation of adult prefrontal and hippocampal networks in oscillatory rhythms. This interplay emerges early in life, most likely as an anticipatory template of later cognitive performance. At neonatal age, hippocampal theta bursts drive the generation of prefrontal theta-gamma oscillations. In the absence of direct reciprocal interactions, the question arises of which feedback mechanisms control the early entrainment of prefrontal-hippocampal networks. Here, we demonstrate that prefrontal-hippocampal activity couples with discontinuous theta oscillations and neuronal firing in both lateral entorhinal cortex and ventral midline thalamic nuclei of neonatal rats. However, these two brain areas have different contributions to the neonatal long-range communication. The entorhinal cortex mainly modulates the hippocampal activity via direct axonal projections. In contrast, thalamic theta bursts are controlled by the prefrontal cortex via mutual projections and contribute to hippocampal activity. Thus, the neonatal prefrontal cortex modulates the level of hippocampal activation by directed interactions with the ventral midline thalamus. Similar to the adult task-related communication, theta-band activity ensures the feedback control of long-range coupling in the developing brain.
  
  
  CONCLUSIONS
  Memories are encoded by finely tuned interactions within large-scale neuronal networks. This cognitive performance is not inherited, but progressively matures in relationship with the establishment of long-range coupling in the immature brain. The hippocampus initiates and unidirectionally drives the oscillatory entrainment of neonatal prefrontal cortex, yet feedback interactions that precisely control this early communication are still unresolved. Here, we identified distinct roles of entorhinal cortex and ventral midline thalamus for the functional development of prefrontal-hippocampal interactions. While entorhinal oscillations modulate the hippocampal activity by timing the neuronal firing via monosynaptic afferents, thalamic nuclei act as a relay station routing prefrontal activation back to hippocampus. Understanding the mechanisms of network maturation represents the prerequisite for assessing circuit dysfunction in neurodevelopmental disorders.
authors.affiliation: Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany, and.
authors.forename: Henrike
authors.initials: H
authors.lastname: Hartung
authors.affiliation: Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany, and.
authors.forename: Marco D
authors.initials: MD
authors.lastname: Brockmann
authors.affiliation: Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany, and.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pöschel
authors.affiliation: Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany, and Laboratory of Neural Computation, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, 38068 Rovereto, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: De Feo
authors.affiliation: Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany, and hangop@zmnh.uni-hamburg.de ileana.hanganu-opatz@zmnh.uni-hamburg.de.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Hanganu-Opatz
mesh_terms: D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D018728:Entorhinal Cortex / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000293:injuries / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013266:Stilbamidines / Q000378:metabolism; D013788:Thalamus / Q000293:injuries / Q000502:physiology*; D013997:Time Factors
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D013266:Stilbamidines
keywords: development; directed interactions; networks; oscillations; synchrony