Functional synaptic circuits in the subplate during fetal and early postnatal development of cat visual cortex

Abstract

Among the first postmitotic cells of the cerebral cortex is a special population located below the cortical plate: the subplate neurons. These neurons reach a high degree of morphological maturity during fetal life, well before the neurons of the cortical layers have matured, yet nearly all of these cells die after birth in the cat. Subplate neurons are also known to receive synaptic contacts. Here we have investigated whether these contacts are functional by making intracellular recordings from subplate neurons in cortical slices maintained in vitro. Subplate neurons were identified based on their location and morphology by injecting them with biocytin following the intracellular recordings. At all ages studied between embryonic day 50 and postnatal day 9, electrical stimulation of the optic radiations elicited EPSPs and synaptic and antidromic spikes in subplate neurons, indicating that some of the synapses seen at the ultrastructural level are indeed capable of synaptic transmission. The spiking patterns of 39 morphologically identified subplate neurons were examined by injecting depolarizing current, which revealed that a large majority gave only a single spike or a brief train of spikes in response to maintained depolarization, in contrast to the regular spiking pattern found in many neurons of adult cortex. Biocytin injections into subplate neurons revealed that they are a morphologically heterogeneous population with respect to their dendritic branching patterns; roughly half were inverted pyramids, the classic subplate neuron morphology. The axonal processes of subplate neurons were remarkable in that many not only arborized within the subplate, but also entered the cortical plate and terminated in the marginal zone. At early postnatal ages, these axons also gave off collaterals within cortical layer 4. The results of this study indicate that subplate neurons participate in synaptic microcircuits during development. While the presynaptic identity of the input to subplate neurons is not known conclusively, it is likely that geniculocortical axons, which wait in close proximity to subplate neurons, contribute significantly. The pattern of axonal branching of subplate neurons also implies that information conferred to subplate neurons may be relayed, in turn, to the neurons of cortical layer 4. Finally with the death of subplate neurons, the geniculocortical axons leave the subplate and invade the cortical plate to innervate directly the neurons of layer 4. Thus, subplate neurons may function as a crucial, but transient synaptic link between waiting geniculocortical axons and their ultimate target cells in the cortex.

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

“…Thalamic axons interact with subplate cells via functional synapses (Friauf et al, 1990;Ghosh and Shatz, 1993;Allendoerfer and Shatz, 1994), leading to the proposal that activity-based competition among axons could prune collaterals and determine the site of entry for thalamic axons (Friauf et al, 1990;Ghosh and Shatz, 1993;Allendoerfer and Shatz, 1994) (but see Molnar et al, 2002). In this way, position across the cortical sheet could be determined by an interaction between thalamic axons and subplate cells.…”

A Novel p75NTR Signaling Pathway Promotes Survival, Not Death, of Immunopurified Neocortical Subplate Neurons

“…This approach permits the study of the direct function of p75NTR, as well as the analysis of p75NTR signaling pathways in the absence of other cell types. The majority of immunopurified cells have a pyramidal morphology, typical of subplate neurons in vivo (Friauf et al, 1990;Allendoerfer and Shatz, 1994), and readily extend processes on a fibronectin substrate in vitro (Fig. 2a).…”

“…They are the first cortical neurons to differentiate and become incorporated into functional neuronal circuits, where they are needed for the establishment of thalamocortical connections (Friauf et al, 1990;Ghosh et al, 1990;Ghosh and Shatz, 1993). However, unlike later-generated cortical neurons, large numbers of subplate neurons undergo programmed cell death during early postnatal development (Allendoerfer and Shatz, 1994;Spreafico et al, 1995;Price et al, 1997).…”

Maturation of Cerebral Connections and Fetal Behavior

“…Although experimental models are important for explanation of basic electrophysiological phenomena, 64,5,12,65 the proper timing of developmental events can be studied in humans only. Four-D ultrasonography 3 offers an objective perspective on continuity of behavior from prenatal to postnatal life.…”

“…[5][6][7][8] In humans, that endogeneous cortical network is already present at 8 weeks post conception (WPC), i.e. at the end of embryonic period and the beginning of the fetal life.…”