Hippocampal Lateralization and Synaptic Plasticity in the Intact Rat: No Left-Right Asymmetry in Electrically Induced CA3-CA1 Long-Term Potentiation.

The hippocampus is not a unitary, homogeneous brain area. Anatomical and functional specialization is evident along the septotemporal axis of the structure, and between the left and right hemispheres. In the mouse brain, a left-right asymmetry has been discovered in the plasticity of CA3-CA1 projections originating in the left versus right hippocampus. Presynaptic afferents originating in the left hemisphere-including both uncrossed Schaffer collaterals, and crossed commissural projections to the contralateral CA1-form small, plastic synapses, whereas afferents originating in right CA3 contact larger, less plastic, synapses. Studies using optogenetic techniques to selectively activate fibers originating from one hemisphere in ex vivo slices have revealed that projections originating from left CA3 exhibit a far greater capacity for long-term potentiation (LTP) of synaptic strength than those originating on the right. However, corresponding data from rats are currently unavailable, leaving open the question of species differences in hippocampal symmetry. In the current study, we reanalyzed data from our previous in vivo LTP work to address this issue. We analyzed plasticity in independent Schaffer collateral and commissural projections to CA1 originating from left and right CA3 in male Lister-hooded rats. However, we found no differences in the magnitude and duration of LTP induced in either crossed or uncrossed pathways following high-frequency tetanization of left versus right CA3. This contrast with previous findings may stem from methodological differences between in vivo electrical and ex vivo optogenetic approaches, but may reflect a genuine species difference in the organization and laterality of the rodent CA3-CA1 system.

The postsubiculum and spatial learning: the role of postsubicular synaptic activity and synaptic plasticity in hippocampal place cell, object, and object-location memory.

Visual landmarks exert stimulus control over spatial behavior and the spatially tuned firing of place, head-direction, and grid cells in the rodent. However, the neural site of convergence for representations of landmarks and representations of space has yet to be identified. A potential site of plasticity underlying associations with landmarks is the postsubiculum. To test this, we blocked glutamatergic transmission in the rat postsubiculum with CNQX, or NMDA receptor-dependent plasticity with d-AP5. These infusions were sufficient to block evoked potentials from the lateral dorsal thalamus and long-term depression following tetanization of this input to the postsubiculum, respectively. In a second experiment, CNQX disrupted the stability of rat hippocampal place cell fields in a familiar environment. In a novel environment, blockade of plasticity with d-AP5 in the postsubiculum did not block the formation of a stable place field map following a 6 h delay. In a final behavioral experiment, postsubicular infusions of both compounds blocked object-location memory in the rat, but did not affect object recognition memory. These results suggest that the postsubiculum is necessary for the recognition of familiar environments, and that NMDA receptor-dependent plasticity in the postsubiculum is required for the formation of new object-place associations that support recognition memory. However, plasticity in the postsubiculum is not necessary for the formation of new spatial maps.

Functional connectivity between the thalamus and postsubiculum: analysis of evoked responses elicited by stimulation of the laterodorsal thalamic nucleus in anesthetized rats.

The laterodorsal nucleus (LDN) of the thalamus provides a prominent afferent projection to the postsubiculum (dorsal presubiculum). To characterize synaptic transmission in this pathway, we placed stimulating electrodes in the LDN and recorded fEPSPs elicited in the postsubiculum of urethane-anesthetized rats. LDN stimulation elicited a source-sink dipole between the deep and superficial layers of the postsubiculum, respectively, consistent with anatomical evidence for the termination of thalamic afferents in the superficial layers of the structure, and the existence of deep layer neurons with apical dendrites extending into these layers. Postsubicular fEPSPs were typically 0.5-1.0 mV in amplitude, with a peak latency of approximately 6 ms. Consistent with anatomical observations, the short onset latency of fEPSPs elicited by LDN stimulation, and their ability to follow a 60-Hz train of stimulation, indicate that the projection is monosynaptic. Paired-pulse stimulation revealed pronounced paired-pulse depression that was maximal at 100 ms, suggesting that initial release probabilities are high at LDN-postsubiculum synapses, in common with many neocortical pathways. A conventional tetanus protocol that yields LTP in hippocampal pathways had no effect on postsubicular fEPSPs, but long-term depression could be induced by 60-Hz stimulation. Drug infusion studies revealed that synaptic transmission in the LDN-postsubiculum projection is predominantly AMPA-receptor mediated. Rats were implanted with indwelling infusion cannulae targeting the postsubiculum, and, after a recovery period, were anaesthetized withurethane, and implanted with stimulating and recording electrodes. Infusion of CNQX almost completely abolished postsubicular fEPSPs, whereas D-AP5 had little effect. However, 60-Hz LTD was blocked by D-AP5 infusion, revealing that this form of synaptic plasticity is NMDA-receptor dependent.