The nucleus of the solitary tract (NTS) contains the central terminations of a broad range of cranial primary afferents that engage homeostatic reflex pathways. These afferent-activated pathways both directly regulate visceral organs (e.g. heart) and indirectly affect integrated responses (e.g. stress or satiety). The heterogeneity of NTS – its various cell types, transmitters, receptors and interconnections with other brain regions – complicates experimental work. Thus, understanding is limited about the mechanisms by which afferent information is conveyed, transformed and then transmitted beyond NTS. Recent work suggests that NTS may be organized quite distinctly depending on the central destination of the afferent information and the evidence suggests that selective deployment of molecular effectors result in distinctly different integrative outcomes. The sources, myelination and modality subtypes of cranial visceral afferents to NTS are diverse across and within organs. Afferents are viscerotopically distributed in NTS and feature characteristic differences in key receptors and enzymes consistent with physically interspersed cohorts of neurons sharing a common property. Understanding this cellular patterning and how it impacts processing seem key to appreciating the broader contributions of NTS neurons to integrated response behaviors. Visceral afferent transmission with NTS relies on glutamatergic mechanisms but overall appears to transgress conventional precepts of central integration of excitation. Central glutamatergic excitatory synapses are: 1. often preferentially deployed on distal dendrites, 2. low in their probability to release vesicles, and 3. relatively weak – properties that generally favor excitation of central neurons by highly redundant, convergent inputs such as at Schaeffer collaterals to CA1 pyramidal cells (Allen and Stevens, 1994). EPSCs from solitary tract (ST) afferents at second order NTS neurons uniformly violate each of these transmission features. ST activation evokes EPSCs that largely rely in non-NMDA receptors and these afferent synapses rarely (<1%) fail to release glutamate. The large amplitude of such currents assures a safety factor of generating an action potential nearly every time and even can endure substantial synaptic depression before attenuating spike output of the second order neurons. Quantal analysis of ST transmission reveals an extraordinarily uniform mechanism that produces a high probability of glutamate release across second order NTS neurons. So with respect to basic glutamate release, ST afferent terminals are remarkably homogeneous, much more so than is common in most brain regions. Another approach in brain slices identifies for study cohorts within NTS by their destination. The approach marries classic neuroanatomical tracers to high resolution electrophysiological recordings (Bailey et al., 2006; Bailey et al., 2007). This work offers a new perspective about homogeneities within NTS sub groups associated with particular central destinations – i.e. NTS projection neurons. While retrograde dyes disclose projection targets, electrophysiology probes functional aspects of circuit organization. Basic properties are probed with pharmacological tools such as capsaicin (CAP) to classify afferents as unmyelinated (CAP-sensitive)(Doyle et al., 2002). Questions include transmitter interactions; voltage-dependent ion channels; and the organization of intra-NTS circuits. Interestingly, the organization and intrinsic cellular differences in myelination subtypes substantially impact information transfer to the central nervous system. Retrograde fluorescent tracers injected into central target regions identify pools of neurons within NTS that project to that particular region. Dye injected into the hypothalamic paraventricular nucleus (PVN) illuminate cohorts of single NTS neurons in vitro with axons projecting to PVN. Likewise, injections within the caudal ventrolateral medulla (CVLM) identify CVLM-projecting NTS neurons. ST activation indicates that all CVLM-projecting NTS neurons were directly connected to ST afferents with an EPSC latency that varied (jitter=S.D.) <200 µsec. In contrast, similar tests of PVN-projecting, medial NTS neurons revealed weaker, polysynaptic intra-NTS excitatory pathways from ST with higher jitter and such neurons expressed substantially larger expression of the A-type, transient potassium channel (IKA). Together, both the convoluted intra-NTS pathway as well as the elevated IKA expression attenuated the afferent information content sent to PVN compared to that via the CVLM pathway. Overall, projection target information identifies relatively homogeneous populations of neurons within the more general heterogeneity of neurons that dominates views of NTS.