Actions of Excitatory and Inhibitory Neurotransmitters

Some neu­rons in the CNS release neu­ro­trans­mit­ters that excite other neu­rons (mean­ing to fire off APs) and some inhibit (pre­vent) the gen­er­a­tion of action potentials.

Action of Exci­ta­tory Neurotransmitters

Presy­nap­tic neu­rons are the neu­rons that con­duct the AP to release a neu­ro­trans­mit­ter and they affect the post­sy­nap­tic neu­rons. What ALWAYS causes a neu­ron to release any neu­ro­trans­mit­ter (whether it is exci­ta­tory or inhibitory) is an action potential.

Ques­tion and reminder: Where are most of the potas­sium ions nor­mally found in the body?

Most are found inside the cells and of course there are neg­a­tively charged pro­teins inside the cell.

Where are most of the sodium ions found?

Out­side the cell. There is an excess of neg­a­tive charges inside and excess of pos­i­tive out­side  and this is known as the rest­ing state).

ALL exci­ta­tory neu­ro­trans­mit­ters cause an open­ing of ligand-gated sodium ion chan­nels.  As a result, sodium ions flow in and the cell becomes less neg­a­tive on the inside.  When we talk about acetyl­choline, it acti­vates ACh recep­tor sites and lig­and gated sodium ion chan­nels open.  These exci­ta­tory neu­ro­trans­mit­ters cre­ate a local increase of per­me­abil­ity of sodium ion chan­nels (lig­and gated sodium chan­nels open) which leads to a local depo­lar­iza­tion that’s known as an Exci­ta­tory Post­sy­nap­tic Poten­tial (EPSP) because we are excit­ing the post-synaptic cell.  So whether the exci­ta­tory neu­ro­trans­mit­ter is dopamine or nor­ep­i­neph­rine or any­thing else, it’s going to always open up ligand-gated sodium ion chan­nels, caus­ing the inside to be less negative.

Action of Inhibitory Neurotransmitters

If an action poten­tial goes down the synap­tic knob of another neu­ron and releases an inhibitory neu­ro­trans­mit­ter, it’s going to be acti­vat­ing specif­i­cally dif­fer­ent recep­tor sites on the cell mem­brane of the post­sy­nap­tic cell.

When an inhibitory NT acti­vates the recep­tor site, it causes addi­tional potas­sium chan­nels to open which may cause potas­sium ions to flow out of the cell and if addi­tional pos­i­tively charged potas­sium ions flow out of the cell, the inside of the cell will become more negative.

In other words, inhibitory neu­ro­trans­mit­ters cause an open­ing of ligand-gated potas­sium ion chan­nels which leads to a local hyper­po­lar­iza­tion (more neg­a­tive than nor­mal).  This is known as a Inhibitory Post­sy­nap­tic Poten­tial (IPSP) because it’s going to be LESS likely to throw off an action potential.

Con­trast that with exi­ta­tory NTs: All exci­ta­tory neu­ro­trans­mit­ters cause an open­ing of ligand-gated sodium ion channels.

The inhibitory NT could also cause an open­ing up of ligand-gated Chlo­ride Ion chan­nels. Chlo­ride is mostly out­side the cell and it’s neg­a­tively charged. When these chan­nels open, neg­a­tively charged ions will flow inside the cell, mak­ing it more neg­a­tive (local hyperpolarization).

Whether potas­sium ions go out the cell or chlo­ride ions go in the cell, the cell becomes hyperpolarized.

Sum­ma­tion of Post-Synaptic Potentials

So what’s this post­sy­nap­tic neu­ron going to do if both these EPSP and IPSP’s are fir­ing off together? It depends on the sum of all these influ­ences. Whether a neu­ron gen­er­ates an Action Poten­tial, or not, this depends on the over­all sum of EPSP’s and IPSP’s occur­ring in the neu­ron at any moment in time.

Remem­ber how gen­er­at­ing an AP is like push­ing a boul­der over a cliff to get it over the thresh­old? With EPSP’s and IPSP’s we have peo­ple (exci­ta­tory NT’s) push­ing the boul­der uphill, try­ing to push it over try­ing to gen­er­ate a AP and we also have oth­ers (the inhibiti­tory NT’s) push­ing it the other way.

Over­sim­pli­fied stu­pid example

Let’s say there’s a neu­ron in my brain that deter­mines whether I buy pizza or not…

Let’s pre­tend it’s an interneu­ron (since those are involved with mem­ory, learn­ing, and deci­sion mak­ing). Imag­ine some­one walks in with fresh pizza and I go “Wow I want pizza!” It’s going to be push­ing the action poten­tial of that neu­ron to the edge. Then you think maybe I shouldn’t cause I just ate and I’m not even hun­gry! But then I smell the pizza and I really want it again. Now I’m think­ing I have only $2 on me so I really shouldn’t buy the pizza. So should I? There’s fac­tors telling me I should and shouldn’t buy the pizza.

The point is, the way our ner­vous sys­tem allows us to make deci­sions are with the sum­ma­tion of Exci­ta­tory Post­sy­nap­tic Poten­tials (EPSP) and Inhibitory Post­sy­nap­tic Poten­tials (IPSP). It’s like the devil and angel on the shoulders-act.

Tem­po­ral summation

  • Tem­po­ral sum­ma­tion is the sum­ma­tion of EPSP’s or IPSP’s due to repeated stim­u­la­tion by one neu­ron.
  • Stim­uli applied to the same axon suf­fi­ciently close together in time add together to depo­lar­ize the membrane.

Look at the pic­ture on the right.  The Y-axis of the graphs are Mem­brane Poten­tial (mV) and it shows that the cell starts out with –70.

At the bot­tom graph, when one neu­ron repeat­edly fires, affect­ing a pos synap­tic neu­rons, this is sum­ming in time (tem­po­ral sum­ma­tion) that causes an action potential.

What would’ve hap­pened if neu­ron B released its inhibitory NT repeat­edly? It would hyper­po­lar­ize more and more, mak­ing it more and more neg­a­tive, mak­ing it less and less likely to fire off an AP.

Spa­tial Summation

There’s also some­thing called spa­tial sum­ma­tion which is the sum­ma­tion of EPSP’s or IPSP’s due to stim­u­la­tion by more than one neu­ron simultaneously.

Top graph: Let’s see what causes a local depo­lar­iza­tion (an action potential).

Neu­ron #1 releases, Neu­rons #2 releases, Neu­ron #3 releases.  Then Neu­rons 1 and 2 release.  When Neu­rons 1+2+3 release at the same time, the sodium chan­nels open, we go beyond the thresh­old poten­tial and have an action potential.

Ques­tion: What if neu­ron A released its exci­ta­tory NT at the same time neu­ron B released its inhibitory NT?

Answer: They would can­cel out and there wouldn’t be much difference.