Development of basal forebrain projections to visual cortex: Dil studies in rat

Abstract

We performed experiments using retrograde and anterograde labeling with DiI to examine the development of basal forebrain (BFB) projections to the visual cortex in postnatal rats. DiI placed in occipital cortex led to retrograde labeling of BFB neurons as early as postnatal day 0 (P0); labeled cells were found mainly in the diagonal band complex but also in the medial septum, globus pallidus, and substantia innominata. The retrogradely labeled BFB cells displayed remarkably well-developed dendritic arbors, even in younger animals, and showed increases in soma size, dendritic arbors, and dendritic spines over the first 2 postnatal weeks. DiI placements in the diagonal band led to anterogradely labeled axons in cortex. At early ages (P0-P1), labeled axons were largely confined to white matter. With increasing age, greater numbers of labeled axons were seen in the white matter and in deep cortical layers, and labeled axons extended into superficial layers. The leading edge of labeled fibers reached layer V of visual cortex by P2 and layer IV by P4 and were found throughout the cortical layers by P6. Numbers and densities of labeled axons in visual cortex were greater in older animals, at least through P14. The time of ingrowth of labeled BFB axons into visual cortex indicates that these afferents grow into particular cortical layers after those layers have differentiated from the cortical plate. These data indicate that basal forebrain projections arrive in occipital cortex after cortical lamination is well underway and after the entry of primary thalamocortical projections.

Cultured basal forebrain cholinergic neurons in contact with cortical cells display synapses, enhanced morphological features, and decreased dependence on nerve growth factor

“…The loss of NGF dependence observed as BFCNs matured beyond 33 DIV is consistent with recent in vitro results from Svendsen et al (1994) and with in vivo findings that adult BFCNs were resistant to degeneration after ablation of hippocan:pal or cortical target neurons (Sofroniew et al, 1987(Sofroniew et al, , 1990(Sofroniew et al, , 1993Minger and Davies, 1992a,b). Taken together with our finding that young ( < 7 DIV) BFCNs also lack NGF dependence in vitro, the critical period of NGF dependence observed in this study roughly parallels the period in vivo (postnatal weeks 1-3) during which BFCNs are developing their axonal projections to cortex (Dinopou10s et al, 1989;Gould et al, 1991;Calarco and Robertson, 1995;De Carlos et al, 1995). During this same period, an increase in NGF production as well as increases in NGF and NGF-receptor mRNA expression have been shown to occur in cortex (Korsching et al, 1985;Large et al, 1986;Shelton and Reichardt, 1986;Whittemore et al, 1986;Koh and Loy, 1989).…”

“…Basal forebrain cholinergic neurons (BFCNs) send a topographically organized axonal projection to the cerebral cortex (Divac, 1975;Wenk et al, 1980;McKinney et al, 1983;Saper, 1984;Calarco and Robertson, 1995). This cholinergc projection is believed to regulate cortical function and to be involved in learning and memory (Bartus and Johnson, 1976;Bartus et al, 1982;Lo Conte et al, 1982;Buzsaki et al, 1988;Buzsaki and Gage, 1989).…”

Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual CortexIn Vivo

“…The low incidence of BFn-induced spindle bursts could be partially attributable to the relative immaturity of the BFn-to-cortex pathway. The distribution of cholinergic fibers in cortical areas shows an adult-like pattern starting at P11 (Calarco and Robertson, 1995). However, we cannot rule out an ineffective stimulation paradigm as a cause for the low incidence of BF-induced oscillations.…”

Connexin hemichannels contribute to spontaneous electrical activity in the human fetal cortex

“…Recent studies performed in the rodent model of cortical development have implicated subplate (SP) neurons as key regulators of early electrical activity and network oscillations (13,14). Their essential role in the establishment of thalamocortical connections and cortical columns (15)(16)(17)(18), extensive connectivity within the early synaptic network (19)(20)(21), and dense gap junction coupling (22,23), as well as the abundant innervation by neuromodulatory transmitter systems (24,25), put SP neurons in an ideal position to synchronize cortical activity during early development. Disruptions to the SP zone during development have been implicated in several major neurological disorders including schizophrenia, cerebral palsy, and autism (26,27).…”