Ultrastructural analysis of parvalbumin synapses in human dorsolateral prefrontal cortex
In the human and nonhuman primate DLPFC, PV interneuron somata and dendritic and axonal processes are predominately located in layers 3–4, and the latter form Gray's Type II synapses (Conde, Lund, Jacobowitz, Baimbridge, & Lewis, 1994; Hof et al., 1991; Lewis, Cruz, Melchitzky, & Pierri, 2001; Melchitzky, Sesack, & Lewis, 1999; Williams, Goldman‐Rakic, & Leranth, 1992; Woo, Miller, & Lewis, 1997). Previous ultrastructural analyses in monkey DLPFC demonstrated that in both the middle (layers deep 3–4) and superficial (layers 2–superficial 3) laminar zones, PV interneurons synapse onto pyramidal cell dendritic shafts, spines, somata, and axon initial segments (Melchitzky et al., 1999; Williams et al., 1992).
In monkeys, the MD thalamus provides robust, direct afferent inputs to the DLPFC (Barbas, Haswell Henion, & Dermon, 1991; Erickson & Lewis, 2004; Giguere & Goldman‐Rakic, 1988; Goldman‐Rakic & Porrino, 1985; Kievit & Kuypers, 1977; Negyessy & Goldman‐Rakic, 2005). Indeed, the majority of all thalamic input to the monkey DLPFC arises from the MD nucleus of the thalamus (Barbas et al., 1991), and these afferents exuberantly target the middle cortical layers, with sparse and rarely identified afferents in the superficial and deep laminar zones (Barbas et al., 1991; Erickson & Lewis, 2004; Giguere & Goldman‐Rakic, 1988; Negyessy & Goldman‐Rakic, 2005). The axon terminals of MD thalamic projections: (1) contain PV (Munkle, Waldvogel, & Faull, 1999; Negyessy & Goldman‐Rakic, 2005); (2) are glutamatergic (Pirot, Jay, Glowinski, & Thierry, 1994); (3) form Gray's Type I synapses (White, 1986) predominately onto pyramidal cell spines (Melchitzky et al., 1999; Negyessy & Goldman‐Rakic, 2005); and (4) form those synapses exclusively within in the middle laminar zone (layers deep 3–4) (Melchitzky et al., 1999; Negyessy & Goldman‐Rakic, 2005; Williams et al., 1992).
Although the ultrastructural properties of PV thalamocortical and PV interneuron synapses in the monkey DLPFC have been carefully characterized as described above (Melchitzky et al., 1999; Negyessy & Goldman‐Rakic, 2005; Williams et al., 1992), no such characterization exists for the human DLPFC. These data are important to acquire in order to appropriately design and interpret anatomical and functional studies of human DLPFC in disease states. Moreover, the use of experimental and anatomical studies in other species to understand the impact of PV synaptic alterations in human disease requires knowledge of the extent to which nonhuman anatomy reflects that of human. Indeed, differences exist between human and nonhuman primates in prefrontal cortex (PFC) anatomy and PFC‐mediated behaviors (Passingham, 2008; Silbereis, Pochareddy, Zhu, Li, & Sestan, 2016; Vendetti & Bunge, 2014). Consequently, we performed an electron microscopic ultrastructural analysis of PV axonal terminals forming Type I or Type II synapses (putative thalamocortical and interneuron terminals, respectively) in the superficial and middle laminar zones of the human DLPFC.