**2. Synaptic plasticity**

The term *Synaptic plasticity* refers to the activity dependent changes in the efficacy of synaptic communication. Donald Hebb in 1949 developed a hypothesis about the mechanism of learning and memory at the neuronal level. Clinical observations enabled investigators to link human memory dysfunction to the hippocampus (Scoville & Milner, 1957; Olds, 1972). These developments stimulated research in the field of synaptic plasticity in the mammalian brain (Blundon, 2008). Synaptic plasticity has been most extensively studied at the Schaffer-collateral pathway (Bliss, 2011) in the hippocampus, the seat of learning and memory, especially declarative memory. In 1973, Bliss and his associates reported that tetanic stimulation of the perforant pathway of presynaptic fibres resulted in high responses at postsynaptic sites on granule cells at the dentate gyrus region, to electric stimulation. The experiments were conducted *in vivo* with anaesthetized rabbits. They called the effect LTP because of the elevation of the postsynaptic potential, which could serve as a cellular substrate for information storage (Bliss & Lomo, 1973).

synaptic transmission can cause an enhancement in the efficacy of transmission between those neurons, brought about by biochemical changes at the synapses. Accordingly Hebbian conditioning needs both presynaptic and postsynaptic activity for its induction. This was followed by a search for instances where synaptic efficacy is altered. The discovery of Long term potentiation (LTP) by Bliss and Lomo in 1973 (Bliss & Lomo, 1973) was the first demonstration of synaptic plasticity. LTP had all the characteristics necessary for a mechanism responsible for learning and memory and thus gained acceptance as a cellular correlate or cellular model system for learning and memory. Moreover, the cellular system with reduced complexity compared to the animal models was more amenable for interrogations at the molecular level. LTP thus became an essential component of a paradigm in which initial insights on molecular mechanisms are provided by experiments

In addition to the fundamental interest of how learning and memory are performed by brain, the study of synaptic plasticity is also attractive as it could lead to practical applications. The principles governing the workings of the molecular machineries involved in synaptic plasticity could be useful in the design of manmade memory devices. In the case of many CNS disorders, early aberrations at the molecular level are likely to involve synaptic plasticity mechanisms since the initial clinical symptoms very often involve cognitive impairments such as deficits in learning and memory. These mechanisms could be possible targets for early therapeutic intervention, provided they drive further molecular processes leading to the pathology of such diseases. Understanding of the mechanisms of

A major challenge in understanding the molecular mechanisms of synaptic plasticity has been the diversity in the underlying mechanisms in different parts of the brain. The current article has reviewed the literature on molecular mechanisms that are involved in the induction and maintenance of different forms synaptic plasticity, mainly LTP and long term depression (LTD) and has attempted to simplify the scenario by extracting general features possessed by these mechanisms. Impairments in synaptic plasticity that could occur in

The term *Synaptic plasticity* refers to the activity dependent changes in the efficacy of synaptic communication. Donald Hebb in 1949 developed a hypothesis about the mechanism of learning and memory at the neuronal level. Clinical observations enabled investigators to link human memory dysfunction to the hippocampus (Scoville & Milner, 1957; Olds, 1972). These developments stimulated research in the field of synaptic plasticity in the mammalian brain (Blundon, 2008). Synaptic plasticity has been most extensively studied at the Schaffer-collateral pathway (Bliss, 2011) in the hippocampus, the seat of learning and memory, especially declarative memory. In 1973, Bliss and his associates reported that tetanic stimulation of the perforant pathway of presynaptic fibres resulted in high responses at postsynaptic sites on granule cells at the dentate gyrus region, to electric stimulation. The experiments were conducted *in vivo* with anaesthetized rabbits. They called the effect LTP because of the elevation of the postsynaptic potential, which could serve as a

involving LTP which could then be validated in higher animal models.

synaptic plasticity would be of great therapeutic value in such instances.

disease conditions have also been touched upon.

cellular substrate for information storage (Bliss & Lomo, 1973).

**2. Synaptic plasticity** 

Several observations from a variety of species indicate that synaptic plasticity and memory are correlative. Behavioural and *in vitro* studies suggest that activity-induced synaptic modulations, such as LTP, play a role in information storage in the brain. This idea has been proposed as the "synaptic plasticity and memory (SPM) hypothesis" (Martin et al., 2000), and has been a major driving force behind the study of synaptic plasticity. Synaptic plasticity includes both short-term changes in the strength or efficacy of neurotransmission as well as longer-term changes in the structure of synapses (Kandel, 2001). Experimental models of changes in synaptic strength or effectiveness in response to repeated electrical stimulation are thought to mimic physiological plasticity at the neuronal level. The efficacy of synaptic transmission could increase as in LTP or it could decrease as in LTD as a result of plasticity. These modifications in synaptic strength, both positive and negative, distributed across millions of connections among neurons, are believed to form the physical and biochemical substrates for learning and memory.

Hippocampal LTP became a favourite model for the study of learning and memory due to the following reasons. First, there is compelling evidence from studies in rodents and higher primates, including humans, that the hippocampus is a critical component of the neural system involved in various forms of long-term memory. Second, several properties of LTP make it an attractive cellular mechanism for information storage. Like memories, LTP can be generated rapidly and is prolonged and strengthened with repetition. It is also input specific in that it is elicited at the synapses activated by afferent activity and not at adjacent synapses on the same postsynaptic cell (Malenka, 2002).
