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.

Coordinated electrical activity in the olfactory bulb gates the oscillatory entrainment of entorhinal networks in neonatal mice

“…The presence of both direct axonal MTC-to-LEC projections and early patterns of oscillatory activity in OB led to the question of their relevance for the emergence of functional assemblies in the neonatal LEC. In contrast to the documented relevance of entorhinal output for developing limbic circuits (11), the role of sensory inputs for the functional maturation of LEC is still unknown.…”

“…These events had faster frequencies when compared to RR with a peak within theta frequency band (4-12 Hz) (Fig 2D). Given their resemblance in shape and frequency dynamics to previously characterized oscillatory events in neonatal cortical areas (9–11, 35), these events were classified as theta bursts.…”

“…It is tempting to speculate about the potential functions of OB-driven entrainment of LEC during neonatal development, before the emergence of cognitive abilities. Our previous results demonstrated that LEC acts as gatekeeper of prefrontal-hippocampal interactions shortly after birth (11). Discontinuous theta bursts in LEC drive the oscillatory entrainment and time the firing of both prelimbic subdivision of PFC and CA1 area of the intermediate/ventral HP.…”

“…As a consequence of hippocampal theta drive, pyramidal neurons in local prelimbic circuits generate beta-low gamma oscillations (15). Theta coupling between neonatal PFC and HP is controlled by the lateral entorhinal cortex (LEC) that densely projects to both areas (11). The complex organization of limbic circuits at early age raises the question, which mechanisms control the gatekeeper function of LEC during early development.…”

Transient developmental increase of prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice

“…Emergence of oscillation-coupled prefrontal ensembles at a developmental stage when the mice are blind, deaf and lack whisking and motor abilities, is driven by hippocampal theta oscillations 23,31 . They result, on their turn, from activation of lateral entorhinal cortex under the control of olfactory stimuli 32,33 . Excitatory hippocampal projections targeting L5/6 neurons promote interlaminar interactions within mPFC centered on coordinated activation of L2/3 pyramidal neurons.…”