Table 2.

List of explicit assumptions we were compelled to make to complete our assessment. Related assumptions are grouped together; explanatory text accompanies each assumption. The section numbers of the assessment where the assumptions were made are also included.

#	Explicit, Forced Assumption	Section
1	11% of CA1 and CA3 cells are GABAergic interneurons.	3.1
	Experimental observations range from 7–11% (Woodson et al., 1989; Aika et al., 1994). We chose 11% for this assessment after calculating the number of boutons each interneuron would be required to have for all the interneurons to fully cover the GABAergic synapses on all the pyramidal cells.
2	CA1 pyramidal cells are homogeneous.	3.1.1
	CA1 pyramidal cells vary in many properties as a function of factors such as dorsal/ventral location and depth within the pyramidal layer, for example (Mizuseki et al., 2011; Slomianka et al., 2011; Graves et al., 2012). However, in the absence of detailed quantitative information about how the bouton count and dendritic structure of the pyramidal cells varies with these factors, we have considered the bouton counts of a few CA1 pyramidal cells as representative of all pyramidal cells (Esclapez et al., 1999).
3	Each CA1 pyramidal cell synapses only once onto each postsynaptic CA1 pyramidal cell.	3.1.1
4	Each CA1 pyramidal cell connection onto a CA1 interneuron comprises three synapses.	3.1.1
	We made these assumptions to determine the divergence of each CA1 pyramidal cell. Deuchars and Thomson (1996) studied the anatomy of one pyramidal to pyramidal cell pair that was found to have two synapses, but its EPSP amplitude was over twice that of the average and so we concluded that most pyramidal to pyramidal connections comprise one synapse. For the CA1 pyramidal cell to interneuron connections, we based our assumption on an observation that CA1 pyramidal cells generally contact O-LM cells with three synapses each (Biro et al., 2005). However, in the CA3, some pyramidal cell to basket cell connections were observed to include only one synapse (Sik et al., 1993; Gulyas et al., 1993) and the EPSP amplitude range of these connections (Gulyas et al., 1993) was similar to that seen in connections in the CA1 (Ali et al., 1998). Yet, current clamp recordings of pyramidal cell to interneuron connections (bistratified and basket cells) in the CA1 revealed a large enough range in EPSP amplitude to suggest that at least some connections may comprise multiple synapses, especially connections onto bistratified cells (Ali et al., 1998).
5	Observations made in the dorsal CA1 are representative of the whole CA1.	2.2
6	The expression of COUP-TFII in interneurons dorsally is representative of the whole CA1.	3.1.2
	Some properties (marker expression, frequency of certain cell types) vary between dorsal and ventral CA1 (Kosaka et al., 1987; Nomura et al., 1997a,b; Fuentealba et al., 2010). Where possible, we averaged values from both sides. In some cases, only dorsal area observations were available. Therefore, our findings will be more representative of the dorsal CA1.
7	All nNOS+/NPY+ cells are either ivy cells or neurogliaform cells.	3.1.2
8	All nNOS+/NPY+ cells with somata in the stratum oriens or pyramidale are ivy cells.	3.1.2
9	nNOS+/NPY+/reelin+ cells in the stratum radiatum are neurogliaform cells.	3.1.2
10	nNOS+/NPY+/reelin− cells in the stratum radiatum are ivy cells.	3.1.2
11	All ivy cells are nNOS+/NPY+ with somata in the stratum oriens, pyramidale, or radiatum.	3.1.2
12	All α-actinin-2+/CR− cells in the stratum lacunosum-moleculare are neurogliaform cells.	3.1.2
	We considered nNOS and NPY to generally indicate neurogliaform family cells (Price et al., 2005; Fuentealba et al., 2010), though we resorted to different criteria in the stratum lacunosum-moleculare because some nNOS+/NPY+ cells there were found to not be neurogliaform family cells (Price et al. 2005). Ivy and neurogliaform cells have similar marker expression profiles (see Armstrong et al., 2012), so we separated them by layer and reelin expression.
13	Ivy and neurogliaform cells make 10 classical synapses on each postsynaptic cell.	3.1.2
	Most neurogliaform family cell boutons do not participate in classical synapses (i.e., do not have a corresponding postsynaptic element) but instead rely on volume transmission (Olah et al., 2009, in somatosensory cortex). For our convergence calculations, we found it necessary to assume a number of corresponding postsynaptic elements (classical synapses) for each connection. We based this number on a prediction made about classical synapses on observations of neurogliaform cell to pyramidal cell connections in the neocortex (Tamas et al., 2003).
14	All stratum oriens SOM+/CB+ cells projecting to the septum are double projection cells.	3.1.3
	Double projection cells are known to express SOM and CB and to project to the septum (Toth and Freund, 1992; Somogyi and Klausberger, 2005; Jinno et al., 2007). Though there appear to be other, minor groups projecting to the septum (Hajos and Mody, 1997; Katona et al., 1999a; Ferraguti et al., 2005; Jinno, 2009), they have not been shown to express SOM and CB together.
15	All SOM+ cells projecting to the subiculum are either double projection or oriens-retrohippocampal cells.	3.1.3
	Of the projection cells, four types are known to target the subiculum: double projection, oriens-retrohippocampal, radiatum-retrohippocampal, and trilaminar (Klausberger and Somogyi, 2008). We separated these into two groups by their SOM expression.
16	Projection interneurons of the stratum oriens with axons in strata oriens and radiatum have the same number of local boutons as do the so-called back projection cells.	3.1.3
17	Projection interneurons of the stratum oriens with axons in strata oriens and radiatum have the same laminar distribution of local boutons as do conventional bistratified cells.	3.1.3
	For several projection cell types, their cell numbers could be estimated but we had no direct observations of their bouton counts or distribution. Because their axon arbors are similar to those of the so-called back projection cells (both the laminar distribution and the small number of local targets; Sik et al., 1994) and conventional bistratified cells (laminar distribution; Sik et al., 1995), we used information from those types to estimate total bouton counts and distribution respectively, which enabled us to calculate local convergence.
18	All stratum oriens-specific cell types contact their postsynaptic targets with 10 synapses each.	3.1.3
	A light microscopy study of O-LM to pyramidal cell connections showed a range of three to 17 potential synapses per connection (Maccaferri et al., 2000). We took the average of 10 synapses per connection, assuming the potential synapses made actual contact. For projection cells whose axons mainly ramify in the strata radiatum and oriens (formerly known as oriens-bistratified cells), a connection was observed to comprise 10 potential synapses (Maccaferri et al., 2000). Therefore, we assumed that all stratum oriens-specific cells contacted their postsynaptic targets with 10 synapses.
19	The ratio of PV+ basket cells:bistratified cells:axo-axonic cells within the stratum pyramidale is the same as the ratio in other layers.	3.1.4
	In the absence of data about the composition of the PV+ cells in the stratum radiatum and oriens, we assumed it was similar to the stratum pyramidale. Though this assumption may favor PV+ basket cells, the majority of PV+ cells are located in the stratum pyramidale, and so we felt observations made in the stratum pyramidale could be treated as broadly representative of PV+ cells in the whole CA1 without introducing significant error.
20	Axo-axonic cells have an average of 7,200 boutons each.	3.1.4
	We based this assumption on the published divergence of a single axo-axonic cell and on the observed number of synapses made for one connection onto a pyramidal cell (Li et al., 1992).
21	The ratio of PV+:CCK+ basket cell boutons in the entire CA1 is 1.6:1.	3.1.5
	We averaged data regarding the relative frequency of PV+ and CCK+ basket cell boutons on pyramidal cell somata and in the pyramidal layer of the mouse CA1 (Foldy et al., 2010; Wyeth et al., 2010). We took this ratio to be representative of the total number of boutons of each basket cell type in rat CA1, for the purpose of calculating the number of CCK+ basket cells.
22	Only basket cells synapse on the somata of pyramidal cells.	3.3.2
	Though other cell types sometimes synapse on pyramidal cell somata, such as bistratified, ivy, or trilaminar cells (Ferraguti et al., 2005; Buhl et al., 1994a; Fuentealba et al., 2008a), we assumed that their contribution was minor in our calculations of interneuronal convergence onto pyramidal cells.
23	Basket cells in the stratum radiatum are likely CCK+ basket cells.	3.1.5
24	CCK+ basket cells are found in all layers of the CA1.	3.1.5
	Many CCK+ basket cells are located in the stratum radiatum; therefore, we assumed unlabelled basket cells in the stratum radiatum were representative of CCK+ basket cells. However, CCK+ basket cells are also found in every other layer of the CA1, even in the stratum lacunosum-moleculare (Vida et al., 1998).
25	CCK+ SCA and ADI cells are only found in the stratum radiatum; all CCK+ cells that are not basket cells in that layer are SCA or ADI cells.	3.1.5
26	CCK+ PPA cells are only found in the stratum lacunosum-moleculare; all CCK+ cells that are not basket cells in that layer are PPA cells.	3.1.5
27	Of CCK+ cells in the stratum radiatum that are not basket cells, half are SCA cells and half are ADI cells.	3.1.5
	To gain a rough idea of the numbers of CCK+ cell types, we identified them based on their characteristic layer (Klausberger and Somogyi, 2008). However, various CCK+ cell types are found in more than one layer. For example, here we assumed that PPA cells were only in the stratum lacunosum-moleculare, but in reality they are occasionally found in the stratum radiatum (Hajos and Mody, 1997) and even once in the stratum oriens (Klausberger et al., 2005).
28	All CCK+/VIP+ and CCK+/VGLUT3+ GABAergic cells are CCK+ basket cells.	3.1.5
	However, ADI cells have been shown to express VGLUT3 (Klausberger et al., 2005), but it is not known what proportion of them express VGLUT3.
29	CCK+ basket cells do not express CB; all CCK+/CB+ cells are non-basket cell types.	3.1.5
30	All the CCK+/CB− cells in the strata oriens and pyramidale are CCK+ basket cells.	3.1.5
31	Lesser known CCK+ cell types are found in the strata oriens and pyramidale.	3.1.5
	Since no CCK+ basket cells have been found to express CB, we assumed that any CCK+/CB+ cells were not basket cells. Little has been published about the lesser-known CCK+ cell types, so we assumed they made up the remaining non-basket cell types in the strata oriens and pyramidale.
32	The septotemporal and mediolateral bouton distribution of CCK+ basket cells is the same as for PV+ basket cells.	3.1.5
	We made this assumption so that we could extrapolate from the slice data to a full axonal bouton count for CCK+ basket cells, using PV+ basket cell bouton distribution data (Halasy et al., 1996).
33	CCK basket cells make eight synapses per connection with other interneurons.	3.1.5
	We made this assumption because they have been shown to make eight synapses/connection with pyramidal cells in mouse (Foldy et al., 2010). However, it has been shown that PV+ basket cells make only one or a few synapses per connection with interneurons (Sik et al., 1995) despite making many synapses per connection on pyramidal cells (Foldy et al., 2010, in mouse). It is not known whether CCK+ basket cells also display this difference with connections onto interneurons, so we assumed they did not.
34	SCA cell and PPA cell axons are distributed such that approximately 50% of their boutons are located outside of a 400 µm thick slice containing the soma.	3.1.5
	The bouton counts for an SCA cell and for a PPA cell were only available for a 400 µm slice (Vida et al., 1998). To extrapolate this count to a total bouton count for the entire SCA or PPA axon, we compared bouton count data for a bistratified cell in a 400 µm slice (Pawelzik et al. 2002) and in a full axon fill (Sik et al., 1995). We found that, for the bistratified cell, the full axon fill had about double the boutons as the slice, so we assumed the same would be true of the SCA cell axon and the PPA cell axon.
35	All IS cells express CR or VIP or both.	3.1.6
36	All cells that express CR or VIP are IS I, II, or III cells, except for CCK+/VIP+ basket cells and CR+ septally projecting cells.	3.1.6
37	CR+/VIP− cells are IS-I or septally projecting cells, CR−/VIP+ cells are IS-II cells, and CR+/VIP+ cells are IS-III cells.	3.1.6
38	All VIP+ cells are CCK+/VIP+ basket cells or IS cells.	3.1.6
	CR is generally a marker of interneuron specificity, but not all IS cells are known to express CR (Acsady et al., 1996a, 1996b; Gulyas et al., 1996; Somogyi and Klausberger, 2005). Those that do not may express VIP (but so do some basket cells). Therefore, we took CR and VIP to be the most reliable markers of interneuron specificity and considered that the various combinations of the two markers identified different types of IS cells. Enkephalin may also be expressed by IS cells (Fuentealba et al., 2010), but it is also expressed by non-IS cells (Price et al., 2005) so we have not derived any information from its expression.
39	Approximately 10% of GABAergic cells in the CA1 express calbindin.	3.1.7
	It has been previously estimated that 10% of GABAergic cells are CB+ (Freund and Buzsaki, 1996).
40	Averaging the inputs to the CA1 from a CA3a and CA3c cell represents the inputs from an average CA3 cell.	3.2.1
	There are known to be significant differences in bouton count and distribution in pyramidal cells from CA3a and CA3c (Sik et al., 1993; Wittner et al., 2007). Since we had data from both areas, we combined it to calculate the laminar distribution and total CA1 divergence of an average CA3 pyramidal cell.
41	For those cell types for which their ratio of innervation of pyramidal cells to interneurons is unknown, the bouton target ratio of 92:8 (pyramidal cell:interneuron) is adequate.	3.1
	We determined the ratio as described in the methods. This ratio took into account the proportion of pyramidal cells and interneurons as well as their numbers of GABAergic input synapses. In reality, the ratio is likely to be even more skewed towards pyramidal cells because some interneurons receive a significant amount of inhibition from afferent GABAergic neurons.
42	Unless stated otherwise, the proximally projecting cell types only contact postsynaptic pyramidal cells on the basal dendrites in the stratum oriens and proximal apical dendrites in the stratum radiatum.	3.3.4
	Some bistratified cells, ivy, or SCA cells have been shown to make occasional synapses in the strata pyramidale or lacunosum-moleculare (Buhl et al., 1994a; Vida et al., 1998; Szabo et al., 2012), and their contribution to those layers has been quantified here. Those synapses counted as being in the stratum pyramidale, we have assigned to the proximal apical or basal dendrites.
43	Unless stated otherwise, the distally projecting cell types only contact postsynaptic pyramidal cells on the distal apical dendrites in the stratum lacunosom-moleculare.	3.3.5
	This assessment still accounts for some neurogliaform cell boutons in the stratum radiatum (especially because some neurogliaform cells are found in the stratum radiatum, Somogyi et al., 2012) and some O-LM cell boutons in the stratum oriens (Sik et al., 1995), but assumes that PPA cells only synapse in the stratum lacunosum-moleculare since there are no quantitative data about them in other layers.
44	The entorhinal cortex supplies most of the excitatory inputs to the stratum lacunosum-moleculare.	3.2.1
	Though the nucleus reuniens supplies a significant portion of excitatory inputs to the stratum lacunosum-moleculare (Wouterlood et al., 1990), not enough information is yet available to quantify their contribution, so we have assumed that the excitatory inputs to the stratum lacunosum-moleculare are supplied by the entorhinal cortex (Witter et al., 1988).