The subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC) in the brain, and plays a major role in the memory consolidation process. It consists of different types of pyramidal neurons. Based on their firing behavior, these excitatory neurons are classified into strong burst firing (SBF), weak burst firing (WBF) and regular firing (RF) neurons. In the first part of the work, morphological differences in the different neuronal subtypes was explored by biocytin staining after classifying the neurons based on the differences in electrophysiological properties. Detailed morphological properties of these three neuronal subtypes were analyzed using Neurolucida neuron reconstruction method. Unlike the differences in their electrophysiological properties, no difference was found in the morphometric properties of these neuronal subtypes. In the second part of the thesis, experimental results on spike- timing- dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of the juvenile (P15-P19) rat are described. The STDP was studied in the WBF and RF neurons. Causal pairing of a single EPSP with a single back propagating action potential (bAP) at a time interval of 10 ms failed to induce plasticity. However, increasing the number of bAPs in such EPSP-bAP pair to three at 50 Hz (bAP burst) induced LTD in both, the RF, as well as the WBF neurons. Increasing the frequency of action potentials to 150 Hz in the bAP burst during causal pairing also induced LTD in both the neuronal subtypes. However, all other STDP related experiments were performed only with the bAP bursts consisting of 3 bAPs evoked at 50 Hz. Amplitude of the causal pairing induced LTD decreased with increasing time interval between EPSP and the bAP burst. Reversing the order of the EPSP and the bAP burst in the pair induced LTP only with a short time interval of 10 ms. This finding is in contrast to most of the reports on excitatory synapses, wherein the pre-before post (causal) pairing induced LTP and vice-versa. The results of causal and anti-causal pairing were used to plot the STDP curve for the WBF neurons. In the STDP curve observed in these synapses, LTD was observed upto a causal time interval of 30 ms, while LTP was limited to 10 ms time interval. Hence, the STDP curve was biased towards LTD. These results reaffirm the earlier observations that the relative timing of the pre- and postsynaptic activities can lead to multiple types of STDP curves. Next, the mechanism of non-Hebbian LTD was studied in both, the RF and WBF neurons. The involvement of calcium in the postsynaptic neuron in plasticity induction was studied by chelating intracellular calcium with BAPTA. The results indicate that the LTD induction in WBF neurons required postsynaptic calcium, while LTD induction in the RF neurons was independent of postsynaptic calcium. Paired pulse ratio (PPR) experiments suggested the involvement of a presynaptic mechanism in the induction of LTD in the RF neurons, and not in the WBF neurons since the PPR was unaffected by the induction protocol only in the WBF neurons. LTD induction in the WBF neurons required activity of the NMDA receptors since LTD was not observed in the presence of the NMDA receptor blocker in the WBF neurons, while it was unaffected in the RF neurons. However, the RF neurons required the activity of L-type calcium channels for plasticity induction, since LTD was affected in the presence of the L-type calcium channel blockers, although the WBF neurons did not require the L-type calcium channel activity for plasticity induction. Hence, in addition to a non-Hebbian STDP curve, a novel mechanism of LTD induction has been reported, where L-type calcium channels are involved in a synaptic plasticity that is expressed via change in the release probability. The findings on the STDP in subicular pyramidal neurons may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in it.

GABA is the major inhibitory neurotransmitter in the central nervous system. It binds to two types of receptors –ionotropic GABAA and metabotropic GABAB. The GABAA receptor directly gates a Clionophore that causes hyperpolarization in mature excitatory neurons while GABAB receptor mediates a slower hyperpolarizing response via G-protein coupled receptor (GPCR) activated potassium channels. This signaling mechanism gets further complicated by the heterogeneous GABA receptor subunit composition that influences the response kinetics in the postsynaptic membrane. In this thesis, the focus has been to decipher the role of GABAA receptors in relation to cellular excitability in the subiculum under physiological and pathophysiological conditions. The subiculum, considered as the output structure of hippocampus, modulates information flow from hippocampus to various cortical and sub-cortical areas and has been implicated in learning and memory, rhythm generation and various neurological disorders. It gates hippocampal activity with its well orchestrated and fine tuned intrinsic and local network properties. Over the years many studies have shown the involvement of subiculum in temporal lobe epilepsy where it forms the focal point of epileptiform activities with altered cellular and network properties. The subiculum is characterized by the presence of a significant population of burst firing neurons that lead local epileptiform activity. By virtue of its bursting nature and recurrent connections, it is a potential site for seizure generation and maintenance. Epileptiform activities are dynamic in nature and change temporally and spatially according to the alterations in electrophysiological properties of neurons. Transitions to different electrical activities in neurons following a prolonged challenge with epileptogenic stimulus have been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of electrophysiological phase transitions in the burst firing neurons of the subiculum in an in vitro brain slice model of epileptogenesis. Whole-cell patch clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable phase was followed by a late suppressed phase upon continuous perfusion with epileptogenic 4-amino pyridine and magnesium-free medium. The late suppressed phase was characterized by inhibitory post-synaptic potentials (IPSPs) in pyramidal excitatory neurons and bursting activity in local fast spiking interneurons at a frequency of 0.1-0.8 Hz. The IPSPs were mediated by GABAA receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These IPSPs ceased following a cut between the CA1 and subiculum. Our results suggest the importance of feedforward inhibition in the suppression of epileptiform activity in subiculum to mediate a homeostatic response towards the induced hyper-excitability. GABA release from presynaptic nerve endings activates postsynaptic GABAA receptors, which evoke faster phasic inhibitory postsynaptic currents (IPSCs) and non-inactivating inhibitory tonic current, mediated through extrasynaptic GABAA receptors. These receptors are heteropentameric GABA-gated channels assembled from 19 possible subunits (α1-6, β1-3, γ1-3, δ, π, ρ1-3, θ, and ε). The 2 major subunits involved in tonic GABAA currents in the hippocampus are α5 and δ subunits. Tonic GABAA receptor mediated inhibitory current plays an important role in neuronal physiology as well as pathophysiology such as mood disorders, insomnia, epilepsy, autism spectrum disorders and schizophrenia. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons having hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. In the present study, we show the involvement of α5βγ GABAA receptors in mediating picrotoxin sensitive tonic current in subicular pyramidal neurons using known pharmacological agents that target specific GABAA receptor subunits. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. Our experiments suggest that tonic GABAergic inhibition can actively modulate subthreshold properties of subicular pyramidal neurons including resonance due to HCNchannels that may potentially alter the response dynamics in an oscillating neuronal network.