Local axon collaterals of area CA1 support spread of epileptiform discharges within CA1, but propagation is unidirectional

Abstract

ABSTRACT:CA3 and subiculum are hippocampal formation regions that can initiate seizure activity because each has a substantial intrinsic excitatory connectivity. We studied the intrinsic connectivity of area CA1 by exploring the spread of synchronous population discharges in ventral hippocampal slices from rats using a recording chamber that permitted multiple simultaneous extracellular recordings along all laminae of CA1. Brief single stimulus pulses were applied to stratum oriens (SO) or stratum radiatum (SR) on the CA3 side or the subicular side of CA1. In disinhibited slices, events triggered with SO or SR stimulation on the CA3-side propagated over the proximo-distal extent of CA1 with a maximal conduction velocity of 0.4 m/s, comparable with antidromic conduction velocities within CA1. By contrast, SO or SR stimuli applied on the subicular side of CA1 triggered events that did not spread ''backward'' toward CA3. These events are rapidly decremented in amplitude and duration. Whereas antidromic responses were largest when stimuli were applied on the subicular side of CA1, such responses were not sufficient to trigger epileptiform discharges when excitatory transmission was intact. We conclude that the unidirectional spread of epileptiform activity in area CA1 is the result of an intrinsic axon collateral system where each pyramidal cell has a proportionally larger projection toward subiculum. Although this collateral system is sparse compared with other hippocampal formation regions, its unidirectionality protects against re-entrant activation of CA3 and may be physiologically significant as a relay from proximal CA1 to distal CA1. V

Estimating coupling direction between neuronal populations with permutation conditional mutual information

“…The coupling direction in the CA1-CA3 indicates that the focus is complex and the seizure sources change over the duration of the discharge. It is noted that the propagation direction at the formation of CA1-CA3 seizure is unidirectional, in accordance with previous findings (Orman et al 2008).…”

Emergence of Physiological Oscillation Frequencies in a Computer Model of Neocortex

“…Biological connection densities across and within cell type groupings are believed to cover the wide range of 1–50% in different areas (Thomson et al, 2002; Song et al, 2005; Orman et al, 2008). A typical number of synapses for a baseline simulation was 831,967 out of 17,888,670 (full number of possible connections: n 2  −  n for a fully connected network without self-connections), for an overall density of 4.65%, consistent with densities found in the literature.…”

Monosynaptic excitatory transmission from the hippocampal CA1 region to the subiculum

“…Prior investigations reported several functional properties on the synapses between the CA1 region and the subiculum [21][22][23][24]. In these studies, stimulation of multiple presynaptic inputs was applied with an extracellular electrode to record the synaptic responses.…”

“…Both SubPCs and CA1PCs are involved in spatial information processing as "place cells" [17][18][19][20]. Several studies on the synaptic transmission from the CA1 region to the subiculum have been reported [21][22][23][24] using extracellular stimulation protocols that activate multiple neighboring inputs from CA1PCs simultaneously, but the precise properties of the unitary monosynaptic transmission from a single CA1PC to a SubPC have not yet been provided. Thus on the functional point of view, the subiculum has been less investigated than the other hippocampal regions such as the CA1 and the CA3 regions.…”